nonsteroidal estrogen nonsteroidal estrogen a nonsteroidal estrogen is an estrogen with a nonsteroidal chemical structure. the most well-known example is the stilbestrol estrogen diethylstilbestrol (des). although nonsteroidal estrogens formerly had an important place in medicine, they have gradually fallen out of favor following the discovery of toxicities associated with high-dose des starting in the early 1970s, and are now almost never used. on the other hand, virtually all selective estrogen receptor modulators (serms) are nonsteroidal, with triphenylethylenes like tamoxifen and clomifene having been derived from des, and these drugs remain widely used in medicine for the treatment of breast cancer among other indications. in addition to pharmaceutical drugs, many xenoestrogens, including phytoestrogens, mycoestrogens, and synthetic endocrine disruptors like bisphenol a, are nonsteroidal substances with estrogenic activity. nonsteroidal estrogendrug classdiethylstilbestrol, one of the most well-known nonsteroidal estrogens.class identifierssynonymsnonsteroidal estrogen receptor agonistsatc codeg03cbiological targetestrogen receptors (erα, erβ, mers (e.g., gper, others))chemical classnonsteroidalin wikidata pharmacology nonsteroidal estrogens act as agonists of the estrogen receptors, erα and erβ. affinities of estrogen receptor ligands for the erα and erβ ligandother namesrelative binding affinities (rba, %)aabsolute binding affinities (ki, nm)aaction erαerβerαerβ estradiole2; 17β-estradiol1001000.115 (0.04–0.24)0.15 (0.10–2.08)estrogen estronee1; 17-ketoestradiol16.39 (0.7–60)6.5 (1.36–52)0.445 (0.3–1.01)1.75 (0.35–9.24)estrogen estriole3; 16α-oh-17β-e212.65 (4.03–56)26 (14.0–44.6)0.45 (0.35–1.4)0.7 (0.63–0.7)estrogen estetrole4; 15α,16α-di-oh-17β-e24.03.04.919estrogen alfatradiol17α-estradiol20.5 (7–80.1)8.195 (2–42)0.2–0.520.43–1.2metabolite 16-epiestriol16β-hydroxy-17β-estradiol7.795 (4.94–63)50 ? ?metabolite 17-epiestriol16α-hydroxy-17α-estradiol55.45 (29–103)79–80 ? ?metabolite 16,17-epiestriol16β-hydroxy-17α-estradiol1.013 ? ?metabolite 2-hydroxyestradiol2-oh-e222 (7–81)11–352.51.3metabolite 2-methoxyestradiol2-meo-e20.0027–2.01.0 ? ?metabolite 4-hydroxyestradiol4-oh-e213 (8–70)7–561.01.9metabolite 4-methoxyestradiol4-meo-e22.01.0 ? ?metabolite 2-hydroxyestrone2-oh-e12.0–4.00.2–0.4 ? ?metabolite 2-methoxyestrone2-meo-e1<0.001–<1<1 ? ?metabolite 4-hydroxyestrone4-oh-e11.0–2.01.0 ? ?metabolite 4-methoxyestrone4-meo-e1<1<1 ? ?metabolite 16α-hydroxyestrone16α-oh-e1; 17-ketoestriol2.0–6.535 ? ?metabolite 2-hydroxyestriol2-oh-e32.01.0 ? ?metabolite 4-methoxyestriol4-meo-e31.01.0 ? ?metabolite estradiol sulfatee2s; estradiol 3-sulfate<1<1 ? ?metabolite estradiol disulfateestradiol 3,17β-disulfate0.0004 ? ? ?metabolite estradiol 3-glucuronidee2-3g0.0079 ? ? ?metabolite estradiol 17β-glucuronidee2-17g0.0015 ? ? ?metabolite estradiol 3-gluc. 17β-sulfatee2-3g-17s0.0001 ? ? ?metabolite estrone sulfatee1s; estrone 3-sulfate<1<1>10>10metabolite estradiol benzoateeb; estradiol 3-benzoate10 ? ? ?estrogen estradiol 17β-benzoatee2-17b11.332.6 ? ?estrogen estrone methyl etherestrone 3-methyl ether0.145 ? ? ?estrogen ent-estradiol1-estradiol1.31–12.349.44–80.07 ? ?estrogen equilin7-dehydroestrone13 (4.0–28.9)13.0–490.790.36estrogen equilenin6,8-didehydroestrone2.0–157.0–200.640.62estrogen 17β-dihydroequilin7-dehydro-17β-estradiol7.9–1137.9–1080.090.17estrogen 17α-dihydroequilin7-dehydro-17α-estradiol18.6 (18–41)14–320.240.57estrogen 17β-dihydroequilenin6,8-didehydro-17β-estradiol35–6890–1000.150.20estrogen 17α-dihydroequilenin6,8-didehydro-17α-estradiol20490.500.37estrogen δ8-estradiol8,9-dehydro-17β-estradiol68720.150.25estrogen δ8-estrone8,9-dehydroestrone19320.520.57estrogen ethinylestradiolee; 17α-ethynyl-17β-e2120.9 (68.8–480)44.4 (2.0–144)0.02–0.050.29–0.81estrogen mestranolee 3-methyl ether ?2.5 ? ?estrogen moxestrolru-2858; 11β-methoxy-ee35–435–200.52.6estrogen methylestradiol17α-methyl-17β-estradiol7044 ? ?estrogen diethylstilbestroldes; stilbestrol129.5 (89.1–468)219.63 (61.2–295)0.040.05estrogen hexestroldihydrodiethylstilbestrol153.6 (31–302)60–2340.060.06estrogen dienestroldehydrostilbestrol37 (20.4–223)56–4040.050.03estrogen benzestrol (b2)–114 ? ? ?estrogen chlorotrianisenetace1.74 ?15.30 ?estrogen triphenylethylenetpe0.074 ? ? ?estrogen triphenylbromoethylenetpbe2.69 ? ? ?estrogen tamoxifenici-46,4743 (0.1–47)3.33 (0.28–6)3.4–9.692.5serm afimoxifene4-hydroxytamoxifen; 4-oht100.1 (1.7–257)10 (0.98–339)2.3 (0.1–3.61)0.04–4.8serm toremifene4-chlorotamoxifen; 4-ct ? ?7.14–20.315.4serm clomifenemrl-4125 (19.2–37.2)120.91.2serm cyclofenilf-6066; sexovid151–152243 ? ?serm nafoxidineu-11,000a30.9–44160.30.8serm raloxifene–41.2 (7.8–69)5.34 (0.54–16)0.188–0.5220.2serm arzoxifenely-353,381 ? ?0.179 ?serm lasofoxifenecp-336,15610.2–16619.00.229 ?serm ormeloxifenecentchroman ? ?0.313 ?serm levormeloxifene6720-cdri; nnc-460,0201.551.88 ? ?serm ospemifenedeaminohydroxytoremifene0.82–2.630.59–1.22 ? ?serm bazedoxifene– ? ?0.053 ?serm etacstilgw-56384.3011.5 ? ?serm ici-164,384–63.5 (3.70–97.7)1660.20.08antiestrogen fulvestrantici-182,78043.5 (9.4–325)21.65 (2.05–40.5)0.421.3antiestrogen propylpyrazoletriolppt49 (10.0–89.1)0.120.4092.8erα agonist 16α-le216α-lactone-17β-estradiol14.6–570.0890.27131erα agonist 16α-iodo-e216α-iodo-17β-estradiol30.22.30 ? ?erα agonist methylpiperidinopyrazolempp110.05 ? ?erα antagonist diarylpropionitriledpn0.12–0.256.6–1832.41.7erβ agonist 8β-ve28β-vinyl-17β-estradiol0.3522.0–8312.90.50erβ agonist prinaberelerb-041; way-202,0410.2767–72 ? ?erβ agonist erb-196way-202,196 ?180 ? ?erβ agonist erteberelserba-1; ly-500,307 ? ?2.680.19erβ agonist serba-2– ? ?14.51.54erβ agonist coumestrol–9.225 (0.0117–94)64.125 (0.41–185)0.14–80.00.07–27.0xenoestrogen genistein–0.445 (0.0012–16)33.42 (0.86–87)2.6–1260.3–12.8xenoestrogen equol–0.2–0.2870.85 (0.10–2.85) ? ?xenoestrogen daidzein–0.07 (0.0018–9.3)0.7865 (0.04–17.1)2.085.3xenoestrogen biochanin a–0.04 (0.022–0.15)0.6225 (0.010–1.2)1748.9xenoestrogen kaempferol–0.07 (0.029–0.10)2.2 (0.002–3.00) ? ?xenoestrogen naringenin–0.0054 (<0.001–0.01)0.15 (0.11–0.33) ? ?xenoestrogen 8-prenylnaringenin8-pn4.4 ? ? ?xenoestrogen quercetin–<0.001–0.010.002–0.040 ? ?xenoestrogen ipriflavone–<0.01<0.01 ? ?xenoestrogen miroestrol–0.39 ? ? ?xenoestrogen deoxymiroestrol–2.0 ? ? ?xenoestrogen β-sitosterol–<0.001–0.0875<0.001–0.016 ? ?xenoestrogen resveratrol–<0.001–0.0032 ? ? ?xenoestrogen α-zearalenol–48 (13–52.5) ? ? ?xenoestrogen β-zearalenol–0.6 (0.032–13) ? ? ?xenoestrogen zeranolα-zearalanol48–111 ? ? ?xenoestrogen taleranolβ-zearalanol16 (13–17.8)140.80.9xenoestrogen zearalenonezen7.68 (2.04–28)9.45 (2.43–31.5) ? ?xenoestrogen zearalanonezan0.51 ? ? ?xenoestrogen bisphenol abpa0.0315 (0.008–1.0)0.135 (0.002–4.23)19535xenoestrogen endosulfaneds<0.001–<0.01<0.01 ? ?xenoestrogen keponechlordecone0.0069–0.2 ? ? ?xenoestrogen o,p'-ddt–0.0073–0.4 ? ? ?xenoestrogen p,p'-ddt–0.03 ? ? ?xenoestrogen methoxychlorp,p'-dimethoxy-ddt0.01 (<0.001–0.02)0.01–0.13 ? ?xenoestrogen hptehydroxychlor; p,p'-oh-ddt1.2–1.7 ? ? ?xenoestrogen testosteronet; 4-androstenolone<0.0001–<0.01<0.002–0.040>5000>5000androgen dihydrotestosteronedht; 5α-androstanolone0.01 (<0.001–0.05)0.0059–0.17221–>500073–1688androgen nandrolone19-nortestosterone; 19-nt0.010.2376553androgen dehydroepiandrosteronedhea; prasterone0.038 (<0.001–0.04)0.019–0.07245–1053163–515androgen 5-androstenediola5; androstenediol6173.60.9androgen 4-androstenediol–0.50.62319androgen 4-androstenedionea4; androstenedione<0.01<0.01>10000>10000androgen 3α-androstanediol3α-adiol0.070.326048androgen 3β-androstanediol3β-adiol3762androgen androstanedione5α-androstanedione<0.01<0.01>10000>10000androgen etiocholanedione5β-androstanedione<0.01<0.01>10000>10000androgen methyltestosterone17α-methyltestosterone<0.0001 ? ? ?androgen ethinyl-3α-androstanediol17α-ethynyl-3α-adiol4.0<0.07 ? ?estrogen ethinyl-3β-androstanediol17α-ethynyl-3β-adiol505.6 ? ?estrogen progesteronep4; 4-pregnenedione<0.001–0.6<0.001–0.010 ? ?progestogen norethisteronenet; 17α-ethynyl-19-nt0.085 (0.0015–<0.1)0.1 (0.01–0.3)1521084progestogen norethynodrel5(10)-norethisterone0.5 (0.3–0.7)<0.1–0.221453progestogen tibolone7α-methylnorethynodrel0.5 (0.45–2.0)0.2–0.076 ? ?progestogen δ4-tibolone7α-methylnorethisterone0.069–<0.10.027–<0.1 ? ?progestogen 3α-hydroxytibolone–2.5 (1.06–5.0)0.6–0.8 ? ?progestogen 3β-hydroxytibolone–1.6 (0.75–1.9)0.070–0.1 ? ?progestogen footnotes: a = (1) binding affinity values are of the format "median (range)" (# (#–#)), "range" (#–#), or "value" (#) depending on the values available. the full sets of values within the ranges can be found in the wiki code. (2) binding affinities were determined via displacement studies in a variety of in-vitro systems with labeled estradiol and human erα and erβ proteins (except the erβ values from kuiper et al. (1997), which are rat erβ). sources: see template page. list of nonsteroidal estrogens pharmaceutical stilbestrols: benzestrol, bifluranol, dienestrol, diethylstilbestrol, dimestrol, fosfestrol, furostilbestrol, hexestrol, mestilbol, methestrol, pentafluranol, phenestrol, terfluranol, stilbestrol esters triphenylethylenes: chlorotrianisene, desmethylchlorotrianisene, estrobin (dbe), m2613, triphenylbromoethylene, triphenylchloroethylene, triphenyliodoethylene, triphenylmethylethylene secosteroids (open-ring steroids): allenestrol, allenolic acid, bisdehydrodoisynolic acid, carbestrol, doisynoestrol, doisynolic acid, fenestrel, methallenestril selective erα or erβ agonists: diarylpropionitrile, erb-196, erteberel, ferb 033, gtx-758, prinaberel, propylpyrazoletriol, way-166818, way-214156 others: 2,8-dhhhc, paroxypropione, quadrosilan, tetrahydrochrysene serms like tamoxifen and raloxifene can also be considered to be nonsteroidal estrogens in some tissues. environmental synthetic xenoestrogens: alkylphenols, bisphenols (e.g., bisphenol a), parabens, phthalates, polyhalogenated compounds natural metalloestrogens: cadmium, others mycoestrogens: taleranol (β-zearalanol), α-zearalenol, β-zearalenol, zearalanone, zearalenone, zeranol (α-zearalanol) phytoestrogens: coumestrol, daidzein, deoxymiroestrol, equol, genistein, miroestrol, many others