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| Trade names | Avicis, Avixis, Ell-Cranell Alpha, Pantostin |
| Other names | 17α-Estradiol; 17-Epiestradiol; MX-4509; Estra-1,3,5(10)-triene-3,17α-diol; β-Estradiol (obsolete, misleading)[1] |
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| Routes of administration | Topical |
| Drug class | Estrogen;5α-Reductase inhibitor |
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| Formula | C18H24O2 |
| Molar mass | 272.388 g·mol−1 |
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Alfatradiol, also known as17α-estradiol and sold under the brand namesAvicis,Avixis,Ell-Cranell Alpha, andPantostin, is a weakestrogen and5α-reductase inhibitor medication which is usedtopically in the treatment ofpattern hair loss (androgenic alopecia or pattern baldness) in men and women.[1][2][3][4] It is astereoisomer of theendogenoussteroid hormone and estrogen17β-estradiol (or simplyestradiol).[1]
Alfatradiol is used in form of anethanolic solution for topical application on thescalp. Similarly to other drugs against alopecia, topical ororal, it has to be applied continuously to prevent further hair loss.[5] Regrowth of hair that was already lost is only possible to a limited extent. In general, advanced alopecia does not respond well to medical treatment, which has historically been thought to be a consequence of thehair roots being lost.[6]
A university-led study (including several authors who are advisors to companies such as Pfizer) in 103 women comparing alfatradiol tominoxidil, another topical hair loss treatment, found the latter to be more effective. In contrast to minoxidil, alfatradiol did not result in an increase of hair density or thickness, but only in slowing down or stabilization of hair loss in this study.[7] In an earlier study, no systemic side effects were noted, and 17α-estradiol was found to reduce androgenic hair loss, though it was not effective at growing new hair.[8]
Other efforts of alfatradiol had been directed atneurodegenerative diseases including Parkinson's.[9]
Other hair loss medications includeketoconazole,finasteride, anddutasteride.
Nothing is known about the use of alfatradiol duringpregnancy orlactation, or in patients under 18 years of age. The package leaflet recommends against using it under these circumstances.[10]
Local burning or itching is not an effect of alfatradiol, but of theethanol in the solvent. The solution can stimulatesebum production.[10]
Alfatradiol (17α-estradiol) is distinguished fromestradiol (17β-estradiol), the predominant sex hormone in females, only by thestereochemistry of thecarbon atom 17. In contrast to 17β-estradiol, 17α-estradiol, while it still binds to theestrogen receptor, has less or no feminizingestrogenic activity depending on its dosage and the tissue it is affecting.[11] Alfatradiol acts as an inhibitor of the enzyme5α-reductase, which is responsible for the activation oftestosterone todihydrotestosterone, and which plays a role in regulating hair growth.[5] 17α-Estradiol has been studied as a therapeutic with potential to treat Alzheimer's and Parkinson's disease and other patients with neurodegenerative diseases.[12] 17α-Estradiol (as the sodium salt of its sulfated form) is a minor component (<10%) of historical hormone replacement products (such asconjugated estrogens, brand name Premarin), which have been studied and/or marketed in women and men since the 1930s. A survey of the effects of various forms of 17α-estradiol in humans on biochemical parameters, efficacy, estrogenicity, metabolism, safety, and tolerability has been published.[13]
Alfatradiol binds to theERα andERβ with 58% and 11% of therelative binding affinity of 17β-estradiol.[14] However, it has 100-fold lower estrogenic activity relative to estradiol.[15] On the other hand, alfatradiol has been found to bind to and activate thebrain-expressedER-X with a greaterpotency than estradiol, indicating that it may be the predominantendogenousligand for the receptor.[16] In contrast to estradiol, alfatradiol is not aligand of theG protein-coupled estrogen receptor (affinity >10 μM).[17]
| Ligand | Other names | Relative binding affinities (RBA, %)a | Absolute binding affinities (Ki, nM)a | Action | ||
|---|---|---|---|---|---|---|
| ERα | ERβ | ERα | ERβ | |||
| 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 |
| Δ8-Estradiol | 8,9-Dehydro-17β-estradiol | 68 | 72 | 0.15 | 0.25 | Estrogen |
| Δ8-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 |
| Δ4-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 ofin-vitro systems withlabeled estradiol and humanERα andERβ proteins (except the ERβ values from Kuiper et al. (1997), which are rat ERβ).Sources: See template page. | ||||||
| Estrogen | ERTooltip Estrogen receptorRBATooltip relative binding affinity (%) | Uterine weight (%) | Uterotrophy | LHTooltip Luteinizing hormone levels (%) | SHBGTooltip Sex hormone-binding globulinRBATooltip relative binding affinity (%) |
|---|---|---|---|---|---|
| Control | – | 100 | – | 100 | – |
| Estradiol (E2) | 100 | 506 ± 20 | +++ | 12–19 | 100 |
| Estrone (E1) | 11 ± 8 | 490 ± 22 | +++ | ? | 20 |
| Estriol (E3) | 10 ± 4 | 468 ± 30 | +++ | 8–18 | 3 |
| Estetrol (E4) | 0.5 ± 0.2 | ? | Inactive | ? | 1 |
| 17α-Estradiol | 4.2 ± 0.8 | ? | ? | ? | ? |
| 2-Hydroxyestradiol | 24 ± 7 | 285 ± 8 | +b | 31–61 | 28 |
| 2-Methoxyestradiol | 0.05 ± 0.04 | 101 | Inactive | ? | 130 |
| 4-Hydroxyestradiol | 45 ± 12 | ? | ? | ? | ? |
| 4-Methoxyestradiol | 1.3 ± 0.2 | 260 | ++ | ? | 9 |
| 4-Fluoroestradiola | 180 ± 43 | ? | +++ | ? | ? |
| 2-Hydroxyestrone | 1.9 ± 0.8 | 130 ± 9 | Inactive | 110–142 | 8 |
| 2-Methoxyestrone | 0.01 ± 0.00 | 103 ± 7 | Inactive | 95–100 | 120 |
| 4-Hydroxyestrone | 11 ± 4 | 351 | ++ | 21–50 | 35 |
| 4-Methoxyestrone | 0.13 ± 0.04 | 338 | ++ | 65–92 | 12 |
| 16α-Hydroxyestrone | 2.8 ± 1.0 | 552 ± 42 | +++ | 7–24 | <0.5 |
| 2-Hydroxyestriol | 0.9 ± 0.3 | 302 | +b | ? | ? |
| 2-Methoxyestriol | 0.01 ± 0.00 | ? | Inactive | ? | 4 |
| Notes: Values are mean ± SD or range.ERRBA =Relative binding affinity toestrogen receptors of ratuterinecytosol. Uterine weight = Percentage change in uterine wet weight ofovariectomized rats after 72 hours with continuous administration of 1 μg/hour viasubcutaneously implantedosmotic pumps.LH levels =Luteinizing hormone levels relative to baseline of ovariectomized rats after 24 to 72 hours of continuous administration via subcutaneous implant.Footnotes:a =Synthetic (i.e., notendogenous).b = Atypical uterotrophic effect which plateaus within 48 hours (estradiol's uterotrophy continues linearly up to 72 hours).Sources:[18][19][20][21][22][23][24][25][26] | |||||
Alfatradiol is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name.[2] It is also known as17α-estradiol.[1]
Alfatradiol is marketed under the brand names Avicis, Avixis, Ell-Cranell Alpha, and Pantostin.[2]
Alfatradiol is available inGermany and severalLatin American countries, includingArgentina,Brazil, andMexico.
Alfatradiol administered systemically improved metabolic function, reduced insulin resistance, decreased intra-abdominal fat, and decreased inflammation in old male mice without inducing feminization, suggesting potential usefulness in the treatment oftype 2 diabetes.[27]
