# 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.

## Pharmacology

Nonsteroidal estrogens act as agonists of the estrogen receptors, ERα and ERβ.
vte Affinities of estrogen receptor ligands for the ERα and ERβ :
| Ligand | Other names | Relative binding affinities (RBA, %)$^a$ | Relative binding affinities (RBA, %)$^a$ | Absolute binding affinities (K$_i$, nM)$^a$ | Absolute binding affinities (K$_i$, nM)$^a$ | Action |
| Ligand | Other names | ERα | ERβ | ERα | ERβ | Action |
| Estradiol | E2; 17β-Estradiol | 100 | 100 | 0.115 (0.04–0.24) | 0.15 (0.10–2.08) | Estrogen |
| Estrone | E1; 17-Ketoestradiol | 16.39 (0.7–60) | 6.5 (1.36–52) | 0.445 (0.3–1.01) | 1.75 (0.35–9.24) | Estrogen |
| Estriol | E3; 16α-OH-17β-E2 | 12.65 (4.03–56) | 26 (14.0–44.6) | 0.45 (0.35–1.4) | 0.7 (0.63–0.7) | Estrogen |
| Estetrol | E4; 15α,16α-Di-OH-17β-E2 | 4.0 | 3.0 | 4.9 | 19 | Estrogen |
| Alfatradiol | 17α-Estradiol | 20.5 (7–80.1) | 8.195 (2–42) | 0.2–0.52 | 0.43–1.2 | Metabolite |
| 16-Epiestriol | 16β-Hydroxy-17β-estradiol | 7.795 (4.94–63) | 50 | ? | ? | Metabolite |
| 17-Epiestriol | 16α-Hydroxy-17α-estradiol | 55.45 (29–103) | 79–80 | ? | ? | Metabolite |
| 16,17-Epiestriol | 16β-Hydroxy-17α-estradiol | 1.0 | 13 | ? | ? | Metabolite |
| 2-Hydroxyestradiol | 2-OH-E2 | 22 (7–81) | 11–35 | 2.5 | 1.3 | Metabolite |
| 2-Methoxyestradiol | 2-MeO-E2 | 0.0027–2.0 | 1.0 | ? | ? | Metabolite |
| 4-Hydroxyestradiol | 4-OH-E2 | 13 (8–70) | 7–56 | 1.0 | 1.9 | Metabolite |
| 4-Methoxyestradiol | 4-MeO-E2 | 2.0 | 1.0 | ? | ? | Metabolite |
| 2-Hydroxyestrone | 2-OH-E1 | 2.0–4.0 | 0.2–0.4 | ? | ? | Metabolite |
| 2-Methoxyestrone | 2-MeO-E1 | <0.001–<1 | <1 | ? | ? | Metabolite |
| 4-Hydroxyestrone | 4-OH-E1 | 1.0–2.0 | 1.0 | ? | ? | Metabolite |
| 4-Methoxyestrone | 4-MeO-E1 | <1 | <1 | ? | ? | Metabolite |
| 16α-Hydroxyestrone | 16α-OH-E1; 17-Ketoestriol | 2.0–6.5 | 35 | ? | ? | Metabolite |
| 2-Hydroxyestriol | 2-OH-E3 | 2.0 | 1.0 | ? | ? | Metabolite |
| 4-Methoxyestriol | 4-MeO-E3 | 1.0 | 1.0 | ? | ? | Metabolite |
| Estradiol sulfate | E2S; Estradiol 3-sulfate | <1 | <1 | ? | ? | Metabolite |
| Estradiol disulfate | Estradiol 3,17β-disulfate | 0.0004 | ? | ? | ? | Metabolite |
| Estradiol 3-glucuronide | E2-3G | 0.0079 | ? | ? | ? | Metabolite |
| Estradiol 17β-glucuronide | E2-17G | 0.0015 | ? | ? | ? | Metabolite |
| Estradiol 3-gluc. 17β-sulfate | E2-3G-17S | 0.0001 | ? | ? | ? | Metabolite |
| Estrone sulfate | E1S; Estrone 3-sulfate | <1 | <1 | >10 | >10 | Metabolite |
| Estradiol benzoate | EB; Estradiol 3-benzoate | 10 | ? | ? | ? | Estrogen |
| Estradiol 17β-benzoate | E2-17B | 11.3 | 32.6 | ? | ? | Estrogen |
| Estrone methyl ether | Estrone 3-methyl ether | 0.145 | ? | ? | ? | Estrogen |
| ent-Estradiol | 1-Estradiol | 1.31–12.34 | 9.44–80.07 | ? | ? | Estrogen |
| Equilin | 7-Dehydroestrone | 13 (4.0–28.9) | 13.0–49 | 0.79 | 0.36 | Estrogen |
| Equilenin | 6,8-Didehydroestrone | 2.0–15 | 7.0–20 | 0.64 | 0.62 | Estrogen |
| 17β-Dihydroequilin | 7-Dehydro-17β-estradiol | 7.9–113 | 7.9–108 | 0.09 | 0.17 | Estrogen |
| 17α-Dihydroequilin | 7-Dehydro-17α-estradiol | 18.6 (18–41) | 14–32 | 0.24 | 0.57 | Estrogen |
| 17β-Dihydroequilenin | 6,8-Didehydro-17β-estradiol | 35–68 | 90–100 | 0.15 | 0.20 | Estrogen |
| 17α-Dihydroequilenin | 6,8-Didehydro-17α-estradiol | 20 | 49 | 0.50 | 0.37 | Estrogen |
| Δ$^8$-Estradiol | 8,9-Dehydro-17β-estradiol | 68 | 72 | 0.15 | 0.25 | Estrogen |
| Δ$^8$-Estrone | 8,9-Dehydroestrone | 19 | 32 | 0.52 | 0.57 | Estrogen |
| Ethinylestradiol | EE; 17α-Ethynyl-17β-E2 | 120.9 (68.8–480) | 44.4 (2.0–144) | 0.02–0.05 | 0.29–0.81 | Estrogen |
| Mestranol | EE 3-methyl ether | ? | 2.5 | ? | ? | Estrogen |
| Moxestrol | RU-2858; 11β-Methoxy-EE | 35–43 | 5–20 | 0.5 | 2.6 | Estrogen |
| Methylestradiol | 17α-Methyl-17β-estradiol | 70 | 44 | ? | ? | Estrogen |
| Diethylstilbestrol | DES; Stilbestrol | 129.5 (89.1–468) | 219.63 (61.2–295) | 0.04 | 0.05 | Estrogen |
| Hexestrol | Dihydrodiethylstilbestrol | 153.6 (31–302) | 60–234 | 0.06 | 0.06 | Estrogen |
| Dienestrol | Dehydrostilbestrol | 37 (20.4–223) | 56–404 | 0.05 | 0.03 | Estrogen |
| Benzestrol (B2) | – | 114 | ? | ? | ? | Estrogen |
| Chlorotrianisene | TACE | 1.74 | ? | 15.30 | ? | Estrogen |
| Triphenylethylene | TPE | 0.074 | ? | ? | ? | Estrogen |
| Triphenylbromoethylene | TPBE | 2.69 | ? | ? | ? | Estrogen |
| Tamoxifen | ICI-46,474 | 3 (0.1–47) | 3.33 (0.28–6) | 3.4–9.69 | 2.5 | SERM |
| Afimoxifene | 4-Hydroxytamoxifen; 4-OHT | 100.1 (1.7–257) | 10 (0.98–339) | 2.3 (0.1–3.61) | 0.04–4.8 | SERM |
| Toremifene | 4-Chlorotamoxifen; 4-CT | ? | ? | 7.14–20.3 | 15.4 | SERM |
| Clomifene | MRL-41 | 25 (19.2–37.2) | 12 | 0.9 | 1.2 | SERM |
| Cyclofenil | F-6066; Sexovid | 151–152 | 243 | ? | ? | SERM |
| Nafoxidine | U-11,000A | 30.9–44 | 16 | 0.3 | 0.8 | SERM |
| Raloxifene | – | 41.2 (7.8–69) | 5.34 (0.54–16) | 0.188–0.52 | 20.2 | SERM |
| Arzoxifene | LY-353,381 | ? | ? | 0.179 | ? | SERM |
| Lasofoxifene | CP-336,156 | 10.2–166 | 19.0 | 0.229 | ? | SERM |
| Ormeloxifene | Centchroman | ? | ? | 0.313 | ? | SERM |
| Levormeloxifene | 6720-CDRI; NNC-460,020 | 1.55 | 1.88 | ? | ? | SERM |
| Ospemifene | Deaminohydroxytoremifene | 0.82–2.63 | 0.59–1.22 | ? | ? | SERM |
| Bazedoxifene | – | ? | ? | 0.053 | ? | SERM |
| Etacstil | GW-5638 | 4.30 | 11.5 | ? | ? | SERM |
| ICI-164,384 | – | 63.5 (3.70–97.7) | 166 | 0.2 | 0.08 | Antiestrogen |
| Fulvestrant | ICI-182,780 | 43.5 (9.4–325) | 21.65 (2.05–40.5) | 0.42 | 1.3 | Antiestrogen |
| Propylpyrazoletriol | PPT | 49 (10.0–89.1) | 0.12 | 0.40 | 92.8 | ERα agonist |
| 16α-LE2 | 16α-Lactone-17β-estradiol | 14.6–57 | 0.089 | 0.27 | 131 | ERα agonist |
| 16α-Iodo-E2 | 16α-Iodo-17β-estradiol | 30.2 | 2.30 | ? | ? | ERα agonist |
| Methylpiperidinopyrazole | MPP | 11 | 0.05 | ? | ? | ERα antagonist |
| Diarylpropionitrile | DPN | 0.12–0.25 | 6.6–18 | 32.4 | 1.7 | ERβ agonist |
| 8β-VE2 | 8β-Vinyl-17β-estradiol | 0.35 | 22.0–83 | 12.9 | 0.50 | ERβ agonist |
| Prinaberel | ERB-041; WAY-202,041 | 0.27 | 67–72 | ? | ? | ERβ agonist |
| ERB-196 | WAY-202,196 | ? | 180 | ? | ? | ERβ agonist |
| Erteberel | SERBA-1; LY-500,307 | ? | ? | 2.68 | 0.19 | ERβ agonist |
| SERBA-2 | – | ? | ? | 14.5 | 1.54 | ERβ agonist |
| Coumestrol | – | 9.225 (0.0117–94) | 64.125 (0.41–185) | 0.14–80.0 | 0.07–27.0 | Xenoestrogen |
| Genistein | – | 0.445 (0.0012–16) | 33.42 (0.86–87) | 2.6–126 | 0.3–12.8 | Xenoestrogen |
| Equol | – | 0.2–0.287 | 0.85 (0.10–2.85) | ? | ? | Xenoestrogen |
| Daidzein | – | 0.07 (0.0018–9.3) | 0.7865 (0.04–17.1) | 2.0 | 85.3 | Xenoestrogen |
| Biochanin A | – | 0.04 (0.022–0.15) | 0.6225 (0.010–1.2) | 174 | 8.9 | Xenoestrogen |
| 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-Prenylnaringenin | 8-PN | 4.4 | ? | ? | ? | Xenoestrogen |
| Quercetin | – | <0.001–0.01 | 0.002–0.040 | ? | ? | 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 |
| Zeranol | α-Zearalanol | 48–111 | ? | ? | ? | Xenoestrogen |
| Taleranol | β-Zearalanol | 16 (13–17.8) | 14 | 0.8 | 0.9 | Xenoestrogen |
| Zearalenone | ZEN | 7.68 (2.04–28) | 9.45 (2.43–31.5) | ? | ? | Xenoestrogen |
| Zearalanone | ZAN | 0.51 | ? | ? | ? | Xenoestrogen |
| Bisphenol A | BPA | 0.0315 (0.008–1.0) | 0.135 (0.002–4.23) | 195 | 35 | Xenoestrogen |
| Endosulfan | EDS | <0.001–<0.01 | <0.01 | ? | ? | Xenoestrogen |
| Kepone | Chlordecone | 0.0069–0.2 | ? | ? | ? | Xenoestrogen |
| o,p'-DDT | – | 0.0073–0.4 | ? | ? | ? | Xenoestrogen |
| p,p'-DDT | – | 0.03 | ? | ? | ? | Xenoestrogen |
| Methoxychlor | p,p'-Dimethoxy-DDT | 0.01 (<0.001–0.02) | 0.01–0.13 | ? | ? | Xenoestrogen |
| HPTE | Hydroxychlor; p,p'-OH-DDT | 1.2–1.7 | ? | ? | ? | Xenoestrogen |
| Testosterone | T; 4-Androstenolone | <0.0001–<0.01 | <0.002–0.040 | >5000 | >5000 | Androgen |
| Dihydrotestosterone | DHT; 5α-Androstanolone | 0.01 (<0.001–0.05) | 0.0059–0.17 | 221–>5000 | 73–1688 | Androgen |
| Nandrolone | 19-Nortestosterone; 19-NT | 0.01 | 0.23 | 765 | 53 | Androgen |
| Dehydroepiandrosterone | DHEA; Prasterone | 0.038 (<0.001–0.04) | 0.019–0.07 | 245–1053 | 163–515 | Androgen |
| 5-Androstenediol | A5; Androstenediol | 6 | 17 | 3.6 | 0.9 | Androgen |
| 4-Androstenediol | – | 0.5 | 0.6 | 23 | 19 | Androgen |
| 4-Androstenedione | A4; Androstenedione | <0.01 | <0.01 | >10000 | >10000 | Androgen |
| 3α-Androstanediol | 3α-Adiol | 0.07 | 0.3 | 260 | 48 | Androgen |
| 3β-Androstanediol | 3β-Adiol | 3 | 7 | 6 | 2 | Androgen |
| Androstanedione | 5α-Androstanedione | <0.01 | <0.01 | >10000 | >10000 | Androgen |
| Etiocholanedione | 5β-Androstanedione | <0.01 | <0.01 | >10000 | >10000 | Androgen |
| Methyltestosterone | 17α-Methyltestosterone | <0.0001 | ? | ? | ? | Androgen |
| Ethinyl-3α-androstanediol | 17α-Ethynyl-3α-adiol | 4.0 | <0.07 | ? | ? | Estrogen |
| Ethinyl-3β-androstanediol | 17α-Ethynyl-3β-adiol | 50 | 5.6 | ? | ? | Estrogen |
| Progesterone | P4; 4-Pregnenedione | <0.001–0.6 | <0.001–0.010 | ? | ? | Progestogen |
| Norethisterone | NET; 17α-Ethynyl-19-NT | 0.085 (0.0015–<0.1) | 0.1 (0.01–0.3) | 152 | 1084 | Progestogen |
| Norethynodrel | 5(10)-Norethisterone | 0.5 (0.3–0.7) | <0.1–0.22 | 14 | 53 | Progestogen |
| Tibolone | 7α-Methylnorethynodrel | 0.5 (0.45–2.0) | 0.2–0.076 | ? | ? | Progestogen |
| Δ$^4$-Tibolone | 7α-Methylnorethisterone | 0.069–<0.1 | 0.027–<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
### Synthetic
#### 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-dihydroxyhexahydrochrysene (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