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Rocha, M.J.; Rocha, E. Synthetic Progestins in Waste and Surface Waters. Encyclopedia. Available online: https://encyclopedia.pub/entry/21924 (accessed on 03 July 2024).
Rocha MJ, Rocha E. Synthetic Progestins in Waste and Surface Waters. Encyclopedia. Available at: https://encyclopedia.pub/entry/21924. Accessed July 03, 2024.
Rocha, Maria João, Eduardo Rocha. "Synthetic Progestins in Waste and Surface Waters" Encyclopedia, https://encyclopedia.pub/entry/21924 (accessed July 03, 2024).
Rocha, M.J., & Rocha, E. (2022, April 19). Synthetic Progestins in Waste and Surface Waters. In Encyclopedia. https://encyclopedia.pub/entry/21924
Rocha, Maria João and Eduardo Rocha. "Synthetic Progestins in Waste and Surface Waters." Encyclopedia. Web. 19 April, 2022.
Synthetic Progestins in Waste and Surface Waters
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This entry is adapted from the peer-reviewed paper 10.3390/toxics10040163

Synthetic progestins (PGs) are a large family of hormones used in continuously growing amounts in human and animal contraception and medicinal therapies. Because wastewater treatment plants (WWTPs) are unable to eradicate PGs after excretion, they are discharged into aquatic systems, where they can also be regenerated from conjugated PG metabolites. The PGs were considered of particular interest due to their wide use, activity, and hormonal derivation (from testosterone, progesterone, and spirolactone). It is concluded that PGs had been analysed in WWTPs influents and effluents and, to a lesser extent, in other matrices, including surface waters, where their concentrations range from ng/L to a few µg/L. Because of their high affinity for cell hormone receptors, PGs are endocrine disruptor compounds that may alter the reproductive fitness and development of biota.

drospirenone EDCs estranes gestagens gonanes norpregnanes pregnanes risk assessment

1. Introduction

Due to water’s vital importance for life, its availability, quality, and governance have been the subject of intense concern, conflicting interests, and heated debate involving communities, industries, governments, and the media [1]. Nonetheless, past actions and the uncontrolled spread of human activities continue to impact water quality and, more broadly, the vast global aquatic ecosystems [2]. One contemporaneous problem widely recognised as serious for mankind is water pollution, including the increase of the concentrations of compounds defined as micropollutants [3][4].
Water micropollutants are currently mostly anthropogenic in origin and include natural and synthetic compounds that enter the aquatic compartment at concentrations ranging from ng/L to µg/L [5]. Among these contaminants are endocrine disruptor compounds (EDCs). Many of them are active ingredients in hormonal medicines, such as synthetic progestins (also called gestagens, progestogens, or progestins), being of particular concern because they are massively used and designed to act in extremely low dosages in specific cellular receptors [6][7].
In humans, progestins (PGs) are used instead of progesterone in endocrine therapy due to the rapid metabolisation of the latter hormone [8]. These substances are used not only as contraceptives, as PGs can inhibit ovulation and the proliferation of the endometrium, but also to treat and prevent endometrial hyperplasia and carcinoma [9][10], to control dysfunctional uterine bleeding [11], and even to stimulate the appetite of cancer patients [12]. In veterinary medicine and zootechny, these compounds are also used in therapies of cows and mares (viz. in disorders of the reproductive system) and for estrus synchronisation and preparation of donor and receptor animals in cases of embryo transfer [13].

2. Classification and Properties of the Most Prominent PGs in Aquatic Environments

PGs are typically classified considering their structural derivation and “generation” (Table 1). The latter broadly indicates when PGs were introduced to the market. Thus, to understand the effects of PGs, the most relevant classification system is to group them by structure based on the steroid molecule from which they were created; i.e., testosterone, progesterone, and spironolactone [14].
Table 1. Pharmacological groups of the selected progestins referred to in this research considering their structural derivation, generation, and androgenic effects in humans: (+++) highly androgenic; (++) medium androgenic; (+) low androgenic; (-) no androgenic effects.
Hormone Family Common Name (Acronym) & CAS Structure
& Molecular Formula		 Generation
& Activity
Toxics 10 00163 i001
19-Nortestosterone		 Gonanes (C17)
Toxics 10 00163 i002
or
LNG family		 Gestodene (GES)
60282-87-4		 Toxics 10 00163 i003
C21H28O2		 3rd Generation
1986
(+++)
Levonorgestrel (LNG)
797-63-7		 Toxics 10 00163 i004
C21H28O2		 2nd Generation
1966
(+++)
Norgestrel (NET)
6533-00-2		 Toxics 10 00163 i005
C21H28O2		 2nd Generation
1966
(+++)
Etonogestrel (ENG)
54048-10-1		 Toxics 10 00163 i006
C22H28O2		 3rd Generation
1998
(+)
Estranes (C18)
Toxics 10 00163 i007
or
NTD family		 Norethisterone (NTD)
68-22-4		 Toxics 10 00163 i008
C20H26O2		 1st Generation
1951
(++)
Norethisterone acetate
(NTDA)
51-98-9		 Toxics 10 00163 i009
C22H28O3		 1st Generation
1951
(++)
Dienogest (DIE)
65928-58-7		 Toxics 10 00163 i010
C22H28O2		 4th Generation
1978
(-)

Progesterone derivatives		 Toxics 10 00163 i011
19-Norprogesterone		 Norpregnanes (C20)
Toxics 10 00163 i012		 Nomegestrol acetate (NOMAC)
58652-20-3		 Toxics 10 00163 i013
C23H30O4		 4th Generation
1986
(-)
Toxics 10 00163 i014
17α-Hydroxyprogesterone		 Pregnanes (C21)
Toxics 10 00163 i015		 Medroxyprogesterone
(MEP)
520-85-4		 Toxics 10 00163 i016
C22H32O3		 1st Generation
1957
(+)
Medroxyprogesterone acetate (MPA)
71-58-9		 Toxics 10 00163 i017
C24H34O4		 1st Generation
1957
(+)
Megestrol acetate
(MGA)
595-33-5		 Toxics 10 00163 i018
C22H30O4		 1st Generation
1963
(-)
Spironolactone
derivative		 Toxics 10 00163 i019
Spironolactone		 Drospirenone (DSP)
67392-87-4		 Toxics 10 00163 i020
C24H30O3		 4th Generation
1976
(-)
Most of the older PGs were designed during the 1960–1970s and have antigonadotrophic effects [15]. The testosterone derivatives, the “gonanes and estranes”, also referred to as levonorgestrel (LNG) and norethisterone (NTD) families [16], have variate activities (Table 1). The gonanes, such as gestodene (GES), norgestrel (NET), and more specifically, its active stereoisomer levonorgestrel (LNG), have high androgenic effects [17]. In contrast, etonogestrel (ENG), which is the biologically active metabolite of desogestrel, is an agonist of the progesterone receptor (PR), showing low androgenic activity and simultaneous glucocorticoid effects [18].
The estranes, NTD and norethisterone acetate (NTDA), have medium androgenic activity [17]. Dienogest (DIE), classified as a fourth generation progestin, is highly specific for the PR [19] and has no androgenic activity [20]. DIE is usually known as a hybrid progestin, as it has the chemical structure of 19-nortestosterone derivatives but shows antiandrogenic activity characteristics, which are typical of progesterone derivatives [20].
The progesterone derivatives, such as those closely related to 19-norprogesterone, which includes nomegestrol acetate (NOMAC), are called “pure” progestational molecules as they bind almost exclusively to the PR and do not interfere with another steroid receptor [19].
In contrast, those PGs derived from 17-hydroxyprogesterone exhibit varying activities. Thus, medroxyprogesterone acetate (MPA) and its metabolite medroxyprogesterone (MEP) have slight androgenic action and exert glucocorticoid activity when given at high doses [21]. Megestrol acetate (MGA) has 50% fewer glucocorticoid effects than MPA [15]. These PGs also act in specific areas of the hypothalamus as antiandrogenic molecules [22]. This action control male sexual behaviour and urine marking—typical of several animals [22]. Moreover, while designed as a PR agonist, MPA has a high binding affinity for glucocorticoid receptors [23][24].
Usually, the most recent PGs derived from progesterone are progestational PGs without androgenic, estrogenic, or glucocorticoid activity. These PGs were conceived to mimic the benefits of progesterone without the undesirable effects of older PGs, such as acne, a decrease in high-density lipoprotein cholesterol (HDL-C), or bloating and water retention [15].
Drospirenone (DSP) is an aldosterone antagonist derived from spironolactone. The primary effect of the latter PG is its anti-mineralocorticoid activity, which causes decreased salt and water retention, leading to lower blood pressure and the absence of androgenic effects [25]. Additionally, DSP exhibits partial antiandrogenic activity [26]—a property that may counter the adverse impact of androgens on hair growth, lipid fluctuation patterns, and insulin, and the possible influence of body composition in postmenopausal women [26]. Further details about PGs’ cellular targets and biological activities in humans can be found in the literature [27][28][29][30].
Presently, the newer formulations of PGs usually contain more potent progestins such as DIE, ENG, and DSP due to their specificity for PR and lack of androgenic effects [30].

3. Waste and Surface Waters Concentrations of Synthetic Progestins

PGs are considered emerging micropollutants in aquatic ecosystems, where they are usually present in concentrations in the order of ng/L. However, accurately knowing their concentrations in waters is crucial since such tiny amounts are potentially harmful to (at least) fish [6][7]. Likely because analysing PGs requires trace analytical methods for their extraction and quantification, the number of studies concerning the environmental levels of these compounds is still scarce and, in a majority, focused on the concentrations of these hormones in influents and effluents from wastewater treatment plants (WWTPs).
In addition, the surveyed areas are still limited in space (Figure 1). From 2015 to 2021, most publications were performed in Europe (48%) and North America (24%). In Asia (19%), South America (5%), and Australia (5%), there are fewer details about the levels of synthetic PGs, and in Africa, as far as researchers notice, there are no data on this subject (Figure 1 and Table 2).
Figure 1. Locations in which studies on the levels of the synthetic PGs considered in this research were conducted in the aquatic environment from 2015 to 2021 (map generated from https://mapchart.net/world.html, accessed on 27 December 2021).
Besides, there are also differences concerning the types of PGs analysed. For example, in Europe, the most prevalent PGs in Switzerland [31] were DIE and MPA, whilst in the Czech Republic, it was MGA [32], and in Germany [33], it was DIE. In Asia, a recent study showed LNG, DSP, and dydrogesterone as the most frequently detected PGs in China [34].
Table 2. Concentrations of synthetic progestins in waste and surface waters. Average (Av); not detected (ND); not evaluated (n.e.); quantification method (QM); surface waters (Sw); WWTP influent (WWTPi); WWTP effluents (WWTPe).
Testosterone derivatives (Gonanes) PGs QM Sw
(ng/L)		 WWTPi (ng/L) WWTPe
(ng/L)		 Local (Country) References
GES (1) 0.2 3 1 Basel and canton Zürich WWTPs (Switzerland). [31]
(2) <0.05 <0.38–7.7 <0.29–0.71 Blanice River and WWTPs (Czech Republic). [32]
(2) <0.64 <0.41–7.0 <0.19–<3.5 Several WWTPs
(Czech and Slovak Republics)		 [35]
(1) <0.3 n.e. <1.0 Several WWTPs and rivers (Germany). [33]
(3) <0.2 <3.0 <1.0 Jona River and WWTPs (Switzerland). [36]
(4) <21.5 <21.5 <21.5 Five WWTPs (Portugal). [37]
LNG (1) <2.5–117 493–811 32–39 Langat River Basin (Malaysia). [38]
(5) <2.5 n.e. <2.5 Southeast Queensland (Australia). [39]
(6) 0.85–3.40 n.e. n.e. Lake Balaton (Hungry). [40]
(7) <15 n.e. <15 Two WWTPs in Quebec (Canada). [41]
(2) <0.08 <0.26–<2.1 <0.22–<0.83 Blanice River and WWTPs (Czech Republic). [32]
(2) <0.09 <0.07–<1.2 <0.03–<0.32 Several WWTPs (Czech and Slovak Republics). [35]
(1) <0.05–<0.7 n.e. <0.3–<1.0 Several WWTPs and rivers (Germany). [33]
(1) ND ND–38.4 ND–20.1 Several WWTPs, Quebec (Canada). [42]
(8) <2.5 <5–299 ± 17 <3.0 Québec and Ontario (Canada). [43]
(4) n.e. 2.81 1.37 21 WWTPs (China). [34]
(4) n.e. n.e. <1.0 Several WWTPs effluents (Germany). [44]
NET (4) n.e. n.e. <2.0 Gran Canaria (Spain) [45]
(4) n.e. 11.2 1.92 21 WWTPs (China). [34]
ENG (2) <0.07 <0.28–<1.4 <0.21–<0.89 Blanice River and WWTPs (Czech Republic). [32]
(2) <0.09 <0.25–<1.2 <0.18–<0.94 Several WWTPs (Czech and Slovak Republics). [35]
(1) <0.3 n.e. <0.5 Several WWTPs and rivers (Germany). [33]
(4) n.e. n.e. <1.2 Several WWTPs effluents (Germany). [44]
Testosterone derivatives (Estranes) NTD (1) <2.5–230 1048–1137 218–265 Langat River Basin (Malaysia). [38]
(4) n.e. n.e. <2.0 Gran Canaria (Spain). [45]
(9) ND–5.20 1.02–94.7
Av. = 25.7		 ND–1.68
Av. = 1.25		 Four WWTPs, Shanghai (China). [46]
(5) <0.21–3.1 n.e. n.e. Freshwater aquaculture (China). [47]
(1) <0.3 <3 <0.6 Basel and canton Zürich WWTPs (Switzerland). [31]
(7) <11 n.e. <11 Two WWTPs in Quebec (Canada). [41]
(2) <0.04 <0.02–<0.17 <0.03–0.85 Blanice River and WWTPs (Czech Republic). [32]
(2) <0.01 <0.02–<0.91 <0.02–<4.1 Several WWTPs (Czech and Slovak Republics). [35]
(1) n.e. n.e. <0.40 Pharmaceutical manufacturing facility discharges (USA). [48]
(3) <0.3 <3 <0.6 Jona River and several WWTPs (Switzerland). [36]
(1) <0.1–<0.3 n.e. <1.0 Several WWTPs and rivers (Germany). [33]
(8) 1.7 ± 0.05–2.7 ± 0.17 <4.8 2 ± 0.2–132 ± 2.2 Québec and Ontario (Canada). [43]
(10) <2.3 <2.3 <2.3 Basque Country (Spain). [49]
(1) ND ND–78.8 ND–31.8 Several WWTPs, Quebec (Canada). [42]
(4) n.e. 4.02 0.20 21 WWTPs (China). [34]
(4) n.e. n.e. <1.0 Several WWTPs effluents (Germany). [44]
NTDA (4) n.e. 10.5 0.24 21 WWTPs (China). [34]
(1) <0.3 n.e. <0.5 Several WWTPs and rivers (Germany). [33]
(4) n.e. n.e. <1.0 Several WWTPs (Germany). [44]
DIE (1) <0.3 <0.8 <0.3 Basel and canton Zürich WWTPs (Switzerland). [31]
(3) <0.3 <0.8 <0.3 Jona River and several WWTPs (Switzerland). [36]
(2) <0.09 1.9–11.0 <0.05–1.0 Blanice River and WWTPs (Czech Republic). [32]
(2) <0.04 1.3–12 <0.04–<4.0 Several WWTPs (Czech and Slovak Republics). [35]
(1) <0.02–2.3 n.e. 1.3–4.4 Several WWTPs and rivers (Germany). [33]
(4) n.e. n.e. 0.3–3.7 Several WWTPs effluents (Germany). [44]

Progesterone derivatives		 NOMAC (2) <0.07 <0.08–3.6 <0.03–0.26 Blanice River and WWTPs (Czech Republic). [32]
MEP (5) <0.07–1.3 n.e. n.e. Freshwater aquaculture (China). [47]
(1) <0.6 <6 <3 Basel and canton Zürich WWTPs (Switzerland). [31]
(3) <0.6 <6 <3 Jona River and several WWTPs (Switzerland). [36]
(2) <0.06 <0.02–<0.13 <0.03–0.23 Blanice River and WWTPs (Czech Republic). [32]
(1) ND ND–5.7 ND–2.9 Several WWTPs, Quebec (Canada). [42]
(2) <0.04 <0.01–<0.53 <0.01–0.95 Several WWTPs (Czech and Slovak Republics). [35]
(1) <0.05 n.e. <0.08 Several WWTPs and rivers (Germany). [33]
MPA (5) <0.21–0.31 n.e. n.e. Freshwater aquaculture (China). [47]
(1) <0.1 <0.8 <0.2 Basel and canton Zürich WWTPs (Switzerland). [31]
(2) <0.1 <0.15–4.4 <0.09–0.58 Blanice River and WWTPs (Czech Republic). [32]
(2) <0.01 <0.04–8.1 <0.04–0.38 Several WWTPs (Czech and Slovak Republics). [35]
(3) <0.1 <0.8–5.3 <0.2 Jona River and several WWTPs (Switzerland). [36]
(1) <0.05–0.1 n.e. <0.08–<0.3 Several WWTPs and rivers (Germany). [33]
(4) n.e. 3.09 0.23 21 WWTPs (China). [34]
(4) n.e. n.e. <0.6 Several WWTPs effluents (Germany). [44]
MGA (4) n.e. n.e. <60 Gran Canaria (Spain). [45]
(1) <0.1 <1 <0.6 Basel and canton Zürich WWTPs (Switzerland). [31]
(2) <0.01 0.52–13.0 0.13–1.0 Several WWTPs (Czech and Slovak Republics). [35]
(1) <0.05–<0.2 n.e. <0.06–<0.3 Several WWTPs and rivers (Germany). [33]
(2) <0.07 <0.03–<6.3 <0.06–0.4 Blanice River and WWTPs (Czech Republic). [32]
(7) <6–<20 n.e. n.e. Water bodies in Santa Maria (Brazil). [50]
(4) n.e. 0.84 0.29 21 WWTPs (China). [34]
Spironolactone
derivative		 DSP (6) 0.26–4.30 n.e. n.e. Lake Balaton (Hungry). [40]
(1) <0.3 <4 <1 Basel and canton Zürich WWTPs (Switzerland). [31]
(2) <0.85 0.64–0.77 <0.18–<0.62 Blanice River and WWTPs (Czech Republic). [32]
(2) <0.04 0.34–6.7 <0.07–<0.29 Several WWTPs (Czech and Slovak Republics). [35]
(3) <0.3 <4 <1 Jona River and several WWTPs (Switzerland). [36]
(1) <0.3 n.e. <0.05 Several WWTPs and rivers (Germany). [33]
(4) n.e. 0.69 0.39 21 WWTPs (China). [34]
(4) n.e. n.e. <0.8 Several WWTPs effluents (Germany). [44]
(1) Liquid chromatography with tandem mass spectrometry detection (LC-MS/MS); (2) liquid chromatography-tandem atmospheric pressure chemical ionization/atmospheric pressure photoionization with hybrid quadrupole/orbital trap mass spectrometry operated in high-resolution product scan mode (LC-APCI/APPI-HRPS); (3) high-performance liquid chromatography coupled to a triple quadrupole mass spectrometry (HPLC-MS/MS); (4) ultra-performance liquid chromatography coupled with tandem mass detection (UPLC-MS/MS); (5) gas chromatography with tandem mass spectrometry detection (GC-MS/MS); (6) high-performance liquid chromatography-mass spectrometry (HPLC-MS); (7) liquid chromatography–mass spectrometry (LC-MS); (8) triple quadrupole-linear ion trap mass spectrometer using the sMRM (scheduled multiple reaction monitoring) mode (TripleQuad-LIT-MS); (9) rapid resolution liquid chromatography/tandem mass spectrometry (RRLC-MS/MS); (10) laser diode thermal desorption–tandem mass spectrometry (LDTD–MS/MS).
Here, concerning the 12 PGs in Table 1, the most investigated (%) were NTD (20%) and LNG (14%). There are still less data concerning MPA, DSP (10%), MEP, MGA (9%), GES, DIE (8%), ENG (5%), NTDA (4%), NET (3%), and NOMAC (1%) (Table 2).
Therefore, in an accessible and organised way, this entry compiles the existing data in the bibliography relative to the concentrations of 12 PGs from 2015 to 2021, using the “Web of Science Core Collection” and “PubMed” as primary databases. Thus, Table 2 presents data on the concentrations of these hormones in surface waters and wastewater treatment plants (WWTPs) worldwide, considering their influents and effluents.
Data in Table 2 were gathered from investigations conducted in various geographic locations, with varying PG inputs, and analysed according to well-established analytical techniques, despite the varying detection and quantification levels and accuracies. It is important to stress that some of the surveyed areas in Asia [38][46][47] are densely populated, which may explain the high amounts of PGs measured in surface waters. Therefore, the disparities between studies from distinct regions are not surprising, corresponding to a wide range of concentrations even when including the three compartments of surface waters, WWTP influents, and WWTP effluents.
Despite the differences mentioned, Figure 2 shows that synthetic PGs are still present in surface waters in amounts comparable to those observed in WWTP effluents, which is concerning given that dilution is predicted in surface waters. A similar observation was also noticed in previous studies [6][7]. As a result, one can infer that WWTPs do not effectively remove these compounds and/or that some of them can be regenerated in the aquatic environment by deconjugation phenomena (Figure 3).
Figure 2. Data are expressed in boxplots with the minimum, median, maximum, average (+), and interquartile range Q1–Q3. Dots represent average individual values measured in surface waters (Sw), WWTP influent (WWTPi) and WWTP effluents (WWTPe) around the world concerning PGs derivates from (A) Testosterone (n = 42 Sw, n = 42 WWTPi, and n = 62 WWTPe), (B) Progesterone (n = 23 Sw, n = 22 WWTPi, and n = 29 WWTPe), (C) Spirolactone (n = 7 Sw, n = 7 WWTPi, and n = 9 WWTPe), (D) all PGs as a whole (n = 72 Sw, n = 71 WWTPi and n = 100 WWTPe), (E) all PGs referred in a previous research (n = 4) [7].
Figure 3. Sources and pathways for the occurrence of progestins in the environment. The distributions of PGs were based on Besse and Garric (2009) [51].
In particular, Figure 2A shows that PGs derived from testosterone, besides being evaluated in a higher number of studies, were also the hormones with higher concentrations (up to ≅1 µg/L) in the aquatic environments, where their global load reaches ≅97.0% of all PGs considered in Table 2 vs. 2.49% and 0.57% for progesterone and spironolactone derivatives.
Table 2 reveals that in surface waters, the concentrations of PGs derived from testosterone were typically higher for LNG (<0.05–117 ng/L) and NTD (<0.01–230 ng/L) than those for GES (<0.05–21.5 ng/L), DIE (<0.02–2.3 ng/L), and NTDA (<0.3 ng/L) ≅ ENG (<0.07–<0.3 ng/L). Data concerning NET in surface waters were not available.
In WWTP influents, the concentrations of LNG (<0.07–811 ng/L ) and NTD (<0.02–1137 ng/L) were consistently higher than those of GES (<0.38–<21.5 ng/L), DIE (<0.8–12.0 ng/L) ≅ NET (11.2 ng/L) ≅ NTDA (10.5 ng/L), and ENG (<0.28–<1.4 ng/L).
In WWTP effluents, the highest concentrations were measured for LNG (<0.03–39 ng/L), NTD (<0.03–265 ng/L), followed by GES (<0.19–<21.5 ng/L), DIE (<0.04–4.4 ng/L), NET (<2.0–1.92 ng/L), NTDA (0.24–<1.0 ng/L) ≅ ENG (<0.21–<1.2 ng/L).
Progesterone-derived PGs more commonly exist in surface waters in concentrations ca. 17-fold lower (Figure 2B) than those reported above for the testosterone derivatives. Such PGs showed similar concentrations to those of the natural hormone progesterone, which ranged from ND to 13.67 ng/L [38][40] in surface waters and from <0.04 ng/L to 24.8 ng/L [32][42] in WWTP influents. In WWTPs effluents, the levels of those PGs were lower than those of progesterone (ND to 110 ng/L) [32][43]. Despite this, progesterone-derived PGs concentrations in surface waters are comparable to those in WWTP effluents, much as testosterone-derived PGs. Moreover, the two most prevalent progesterone-derived PGs, MGA and MEP, were found in identical amounts in all three aquatic compartments.

References

  1. Wilson, N.J.; Harris, L.M.; Nelson, J.; Shah, S.H. Re-theorizing politics in water governance. Water 2019, 11, 1470.
  2. Cosgrove, W.J.; Loucks, D.P. Water management: Current and future challenges and research directions. Water Resour. Res. 2015, 51, 4823–4839.
  3. EU Water Initiative (EUWI). Water Scarcity Management in the Context of WFD. 2006, SCG Agenda Point 8b (WGB/15160506/25d). Available online: https://ec.europa.eu/environment/water/quantity/pdf/comm_droughts/8a_1.pdf (accessed on 27 December 2021).
  4. EU. Directive 2000/60/EC of the European Parliament and of the Council of 23 October 2000 establishing a framework for Community action in the field of water policy. Off. J. Eur. Communities 2000, L327, 0001–0073.
  5. Arnold, K.E.; Brown, A.R.; Ankley, G.T.; Sumpter, J.P. Medicating the environment: Assessing risks of pharmaceuticals to wildlife and ecosystems. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2014, 369, 20130569.
  6. Kumar, V.; Johnson, A.C.; Trubiroha, A.; Tumová, J.; Ihara, M.; Grabic, R.; Kloas, W.; Tanaka, H.; Kroupová, H.K. The Challenge presented by progestins in ecotoxicological research: A critical review. Environ. Sci. Technol. 2015, 49, 2625–2638.
  7. Fent, K. Progestins as endocrine disrupters in aquatic ecosystems: Concentrations, effects and risk assessment. Environ. Int. 2015, 84, 115–130.
  8. Stanczyk, F.Z.; Hapgood, J.P.; Winer, S.; Mishell, D.R., Jr. Progestogens used in postmenopausal hormone therapy: Differences in their pharmacological properties, intracellular actions, and clinical effects. Endocr. Rev. 2013, 34, 171–208.
  9. Gambrell, R.D., Jr.; Bagnell, C.A.; Greenblatt, R.B. Role of estrogens and progesterone in the etiology and prevention of endometrial cancer: Review. Am. J. Obstet. Gynecol. 1983, 146, 696–707.
  10. Lobo, R.A. The role of progestins in hormone replacement therapy. Am. J. Obstet. Gynecol. 1992, 166, 1997–2004.
  11. Chuong, C.J.; Brenner, P.F. Management of abnormal uterine bleeding. Am. J. Obstet. Gynecol. 1996, 175, 787–792.
  12. Kornek, G.V.; Schenk, T.; Ludwig, H.; Hejna, M.; Scheithauer, W. Placebo-controlled trial of medroxy—Progesterone acetate in gastrointestinal malignancies and cachexia. Onc. Res. Treat. 1996, 19, 164–168.
  13. EU. The European agency for the evaluation of medicinal products. Eval. Med. Insp. 1999, 33, 969–978.
  14. Apgar, B.S.; Greenberg, G. Using progestins in clinical practice. Am. Fam. Physician 2000, 62, 1839–1846.
  15. Sitruk-Ware, R. New progestagens for contraceptive use. Hum. Reprod. Update 2006, 12, 169–178.
  16. Edgren, R.A.; Stanczyk, F.Z. Nomenclature of the gonane progestins. Contraception 1999, 60, 313.
  17. Mathur, R.; Levin, O.; Azziz, R. Use of ethinylestradiol/drospirenone combination in patients with the polycystic ovary syndrome. Ther. Clin. Risk Manag. 2008, 4, 487–492.
  18. Hohmann, H.; Creinin, M.D. The contraceptive implant. Clin. Obstet. Gynecol. 2007, 50, 907–917.
  19. Sitruk-Ware, R. Pharmacological profile of progestins. Maturitas 2004, 47, 277–283.
  20. Katsuki, Y.; Sasagawa, S.; Takano, Y.; Shibutani, Y.; Aoki, D.; Udagawa, Y.; Nozawa, S. Animal studies on the endocrinological profile of dienogest, a novel synthetic steroid. Drugs Exp. Clin. Res. 1997, 23, 45–62.
  21. Bullock, L.P.; Bardin, C.W. Androgenic, synandrogenic, and antiandrogenic actions of progestins. Ann. N. Y. Acad. Sci. 1977, 286, 321–330.
  22. Seksel, K. Chapter 7—Behavior-modifying drugs. In Small Animal Clinical Pharmacology, 2nd ed.; Maddison, J.E., Page, S.W., Church, D.B., Eds.; W.B. Saunders: Edinburgh, UK, 2008; pp. 126–147.
  23. Moore, N.L.; Hanson, A.R.; Ebrahimie, E.; Hickey, T.E.; Tilley, W.D. Anti-proliferative transcriptional effects of medroxyprogesterone acetate in estrogen receptor positive breast cancer cells are predominantly mediated by the progesterone receptor. J. Steroid Biochem. Mol. Biol. 2020, 199, 105548.
  24. Thomas, C.P.; Liu, K.Z.; Vats, H.S. Medroxyprogesterone acetate binds the glucocorticoid receptor to stimulate α-ENaC and sgk1 expression in renal collecting duct epithelia. Am. J. Physiol. Renal. Physiol. 2006, 290, F306–F312.
  25. Murphy, S.J.; Littleton-Kearney, M.T.; McCullough, L.D.; Hurn, P.D. Sex, hormones and the endothelium. In Advances in Molecular and Cell Biology; Elsevier: Amsterdam, The Netherlands, 2004; Volume 34, pp. 71–84.
  26. Sitruk-Ware, R. Pharmacology of different progestogens: The special case of drospirenone. Climacteric 2005, 8, 4–12.
  27. Schindler, A.E.; Campagnoli, C.; Druckmann, R.; Huber, J.; Pasqualini, J.R.; Schweppe, K.W.; Thijssen, J.H.H. Reprint of Classification and pharmacology of progestins. Maturitas 2008, 61, 171–180.
  28. Fraser, I.S. Non-contraceptive health benefits of intrauterine hormonal systems. Contraception 2010, 82, 396–403.
  29. Regidor, P.-A. The clinical relevance of progestogens in hormonal contraception: Present status and future developments. Oncotarget 2018, 9, 34628–34638.
  30. Allen, R.H.; Kaunitz, A.M.; Hickey, M. Chapter 18—Hormonal Contraception. In Williams Textbook of Endocrinology, 13th ed.; Melmed, S., Polonsky, K.S., Larsen, P.R., Kronenberg, H.M., Eds.; Elsevier: Philadelphia, PA, USA, 2016; pp. 664–693.
  31. Zhang, K.; Zhao, Y.; Fent, K. Occurrence and ecotoxicological effects of free, conjugated, and halogenated steroids including 17α-hydroxypregnanolone and pregnanediol in Swiss. Environ. Sci. Technol. 2017, 51, 6498–6506.
  32. Golovko, O.; Šauer, P.; Fedorova, G.; Kroupová, H.K.; Grabic, R. Determination of progestogens in surface and waste water using SPE extraction and LC-APCI/APPI-HRPS. Sci. Total Environ. 2018, 621, 1066–1073.
  33. Weizel, A.; Schlüsener, M.P.; Dierkes, G.; Ternes, T.A. Occurrence of glucocorticoids, mineralocorticoids, and progestogens in various treated wastewater, rivers, and streams. Environ. Sci. Technol. 2018, 52, 5296–5307.
  34. Yu, Q.; Geng, J.; Zong, X.; Zhang, Y.; Xu, K.; Hu, H.; Deng, Y.; Zhao, F.; Ren, H. Occurrence and removal of progestagens in municipal wastewater treatment plants from different regions in China. Sci. Total Environ. 2019, 668, 1191–1199.
  35. Šauer, P.; Stará, A.; Golovko, O.; Valentová, O.; Bořík, A.; Grabic, R.; Kroupová, H.K. Two synthetic progestins and natural progesterone are responsible for most of the progestagenic activities in municipal wastewater treatment plant effluents in the Czech and Slovak republics. Water Res. 2018, 137, 64–71.
  36. Zhang, K.; Fent, K. Determination of two progestin metabolites (17α-hydroxypregnanolone and pregnanediol) and different classes of steroids (androgens, estrogens, corticosteroids, progestins) in rivers and wastewaters by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Sci. Total Environ. 2018, 610–611, 1164–1172.
  37. Silva, S.; Cardoso, V.V.; Duarte, L.; Carneiro, R.N.; Almeida, C.M.M. Characterization of five Portuguese wastewater treatment plants: Removal efficiency of pharmaceutical active compounds through conventional treatment processes and environmental risk. Appl. Sci. 2021, 11, 7388.
  38. Tan, E.S.S.; Ho, Y.B.; Zakaria, M.P.; Latif, P.A.; Saari, N. Simultaneous extraction and determination of pharmaceuticals and personal care products (PPCPs) in river water and sewage by solid-phase extraction and liquid chromatography-tandem mass spectrometry. Int. J. Environ. Anal. Chem. 2015, 95, 816–832.
  39. King, O.C.; van de Merwe, J.P.; McDonald, J.A.; Leusch, F.D.L. Concentrations of levonorgestrel and ethinylestradiol in wastewater effluents: Is the progestin also cause for concern? Environ. Toxicol. Chem. 2016, 35, 1378–1385.
  40. Avar, P.; Maasz, G.; Takacs, P.; Lovas, S.; Zrinyi, Z.; Svigruha, R.; Takatsy, A.; Toth, L.G.; Pirger, Z. HPLC-MS/MS analysis of steroid hormones in environmental water samples. Drug Test. Anal. 2016, 8, 123–127.
  41. Comtois-Marotte, S.; Chappuis, T.; Vo Duy, S.; Gilbert, N.; Lajeunesse, A.; Taktek, S.; Desrosiers, M.; Veilleux, É.; Sauvé, S. Analysis of emerging contaminants in water and solid samples using high resolution mass spectrometry with a Q Exactive orbital ion trap and estrogenic activity with YES-assay. Chemosphere 2017, 166, 400–411.
  42. Yarahmadi, H.; Duy, S.V.; Hachad, M.; Dorner, S.; Sauvé, S.; Prévost, M. Seasonal variations of steroid hormones released by wastewater treatment plants to river water and sediments: Distribution between particulate and dissolved phases. Sci. Total Environ. 2018, 635, 144–155.
  43. Goeury, K.; Vo Duy, S.; Munoz, G.; Prévost, M.; Sauvé, S. Analysis of Environmental Protection Agency priority endocrine disruptor hormones and bisphenol A in tap, surface and wastewater by online concentration liquid chromatography tandem mass spectrometry. J. Chromatogr. A 2019, 1591, 87–98.
  44. Weizel, A.; Schlüsener, M.P.; Dierkes, G.; Wick, A.; Ternes, T.A. Fate and behavior of progestogens in activated sludge treatment: Kinetics and transformation products. Water Res. 2021, 188, 116515.
  45. Guedes-Alonso, R.; Ciofi, L.; Sosa-Ferrera, Z.; Santana-Rodríguez, J.J.; Bubba, M.d.; Kabir, A.; Furton, K.G. Determination of androgens and progestogens in environmental and biological samples using fabric phase sorptive extraction coupled to ultra-high performance liquid chromatography tandem mass spectrometry. J. Chromatogr. A 2016, 1437, 116–126.
  46. Xu, G.; Ma, S.; Tang, L.; Sun, R.; Xiang, J.; Xu, B.; Bao, Y.; Wu, M. Occurrence, fate, and risk assessment of selected endocrine disrupting chemicals in wastewater treatment plants and receiving river of Shanghai, China. Environ. Sci. Pollut. Res. Int. 2016, 23, 25442–25450.
  47. Liu, S.; Xu, X.R.; Qi, Z.H.; Chen, H.; Hao, Q.W.; Hu, Y.X.; Zhao, J.L.; Ying, G.G. Steroid bioaccumulation profiles in typical freshwater aquaculture environments of South China and their human health risks via fish consumption. Environ. Pollut. 2017, 228, 72–81.
  48. Scott, T.-M.; Phillips, P.J.; Kolpin, D.W.; Colella, K.M.; Furlong, E.T.; Foreman, W.T.; Gray, J.L. Pharmaceutical manufacturing facility discharges can substantially increase the pharmaceutical load to US wastewaters. Sci. Total Environ. 2018, 636, 69–79.
  49. Miossec, C.; Lanceleur, L.; Monperrus, M. Multi-residue analysis of 44 pharmaceutical compounds in environmental water samples by solid-phase extraction coupled to liquid chromatography-tandem mass spectrometry. J. Sep. Sci. 2019, 42, 1853–1866.
  50. Pivetta, G.G.; Gastaldini, M.D.C. Presence of emerging contaminants in urban water bodies in southern Brazil. J. Water Health 2019, 17, 329–337.
  51. Besse, J.-P.; Garric, J. Progestagens for human use, exposure and hazard assessment for the aquatic environment. Environ. Pollut. 2009, 157, 3485–3494.
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