Alfatradiol: Difference between revisions

{{Short description|Medication}}

{{About|17α-estradiol as a medication|its role as a hormone|17α-Estradiol}}

{{Use dmy dates|date=April 2023}}

{{Infobox drug

| Watchedfields = changed

| verifiedrevid = 458276229

| IUPAC_name = (8''R'',9''S'',13''S'',14''S'',17''R'')-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[''a'']phenanthrene-3,17-diol

| alt = Skeletal formula of alfatradiol

| width = 225px

| image2 = Alfatradiol 3D ball.png

| alt2 = Ball-and-stick model of the alfatradiol molecule

| width2 = 225px

| tradename = Avicis, Avixis, Ell-Cranell Alpha, Pantostin

| pregnancy_AU = <!-- A, B1, B2, B3, C, D, X -->

| pregnancy_US = C

| legal_US = Rx-only

| legal_status =

| class = [[Estrogen (medication)|Estrogen]]; [[5α-Reductase inhibitor]]

<!--Pharmacokinetic data-->

| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life =

| excretion =

| ATC_prefix = None

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 61840

| synonyms = 17α-Estradiol; 17-Epiestradiol; MX-4509; Estra-1,3,5(10)-triene-3,17α-diol; β-Estradiol (obsolete, misleading)<ref name="Elks2014" />

| SMILES = OC1CCC3C1(C)CCC(c2cc4)C3CCc2cc4O

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

'''Alfatradiol''', also known as '''17α-estradiol''' and sold under the brand names '''Avicis''', '''Avixis''', '''Ell-Cranell Alpha''', and '''Pantostin''', is a weak [[estrogen (medication)|estrogen]] and [[5α-reductase inhibitor]] medication which is used [[topical medication|topically]] in the treatment of [[pattern hair loss]] (androgenic alopecia or pattern baldness) in men and women.<ref name="Elks2014">{{cite book|author=J. Elks|title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA897|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|page=897}}</ref><ref name="Drugs.com">{{cite web | title = Alfatradiol | url = https://www.drugs.com/international/alfatradiol.html | work = Drugs.com International }}</ref><ref name="Hunnius" /><ref name="WHO" /> It is a [[stereoisomerism|stereoisomer]] of the [[endogeny (biology)|endogenous]] [[steroid hormone]] and estrogen [[17β-estradiol]] (or simply [[estradiol (medication)|estradiol]]).<ref name="Elks2014" />

==Medical uses==

Alfatradiol is used in form of an [[ethanol]]ic solution for topical application on the [[scalp]]. Similarly to other drugs against alopecia, topical or [[Oral administration|oral]], it has to be applied continuously to prevent further hair loss.<ref name="Mutschler" /> 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 the [[hair root]]s being lost.<ref name="Austria-Codex" />

A university-led study (including several authors who are advisors to companies such as Pfizer) in 103 women comparing alfatradiol to [[minoxidil]], 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.<ref name="pmid17451383">{{cite journal | vauthors = Blume-Peytavi U, Kunte C, Krisp A, Garcia Bartels N, Ellwanger U, Hoffmann R | title = Comparison of the efficacy and safety of topical minoxidil and topical alfatradiol in the treatment of androgenetic alopecia in women | journal = Journal der Deutschen Dermatologischen Gesellschaft | volume = 5 | issue = 5 | pages = 391–5 | date = May 2007 | pmid = 17451383 | doi = 10.1111/j.1610-0387.2007.06295.x | s2cid = 10260867 }}</ref> 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.<ref name="pmid7398983">{{cite journal | vauthors = Orfanos CE, Vogels L | title = [Local therapy of androgenetic alopecia with 17 alpha-estradiol. A controlled, randomized double-blind study (author's transl)] | language = de | journal = Dermatologica | volume = 161 | issue = 2 | pages = 124–32 | date = 1980 | pmid = 7398983 | doi = 10.1159/000250344}}</ref>

Other efforts of alfatradiol had been directed at [[neurodegenerative disease]]s including Parkinson's.<ref>{{cite web | title = Alfatradiol | url = https://adisinsight.springer.com/drugs/800020680 | work = Adis Insight}}</ref>

Other hair loss medications include [[ketoconazole]], [[finasteride]], and [[dutasteride]].

Nothing is known about the use of alfatradiol during [[pregnancy]] or [[lactation]], or in patients under 18 years of age. The package leaflet recommends against using it under these circumstances.<ref name="RoteListe" />

==Side effects==

Local burning or itching is not an effect of alfatradiol, but of the [[ethanol]] in the solvent. The solution can stimulate [[sebum]] production.<ref name="RoteListe" />

==Pharmacology==

===Pharmacodynamics===

[[File:17-alpha- vs 17-beta-estradiol.svg|thumb|left|Alfatradiol (top) and 17β-estradiol (bottom).]]

Alfatradiol (17α-estradiol) is distinguished from [[estradiol]] (17β-estradiol), the predominant sex hormone in females, only by the [[stereochemistry]] of the [[carbon]] atom 17. In contrast to 17β-estradiol, 17α-estradiol, while it still binds to the [[estrogen receptor]], has less or no feminizing [[estrogen (medication)|estrogen]]ic activity depending on its dosage and the tissue it is affecting.<ref>{{cite journal | vauthors = Moos WH, Dykens JA, Howell N | year = 2008 | title = 17α-Estradiol: A Less-Feminizing Estrogen | journal = Drug Development Research | volume = 69 | issue = 4| pages = 177–184 | doi=10.1002/ddr.20244| s2cid = 72463459 }}</ref> Alfatradiol acts as an inhibitor of the enzyme [[5α-reductase]], which is responsible for the activation of [[testosterone]] to [[dihydrotestosterone]], and which plays a role in regulating hair growth.<ref name="Mutschler" /> 17α-Estradiol has been studied as a therapeutic with potential to treat Alzheimer's and Parkinson's disease and other patients with neurodegenerative diseases.<ref>{{cite journal | vauthors = Dykens JA, Moos WH, Howell N | title = Development of 17alpha-estradiol as a neuroprotective therapeutic agent: rationale and results from a phase I clinical study | journal = Annals of the New York Academy of Sciences | volume = 1052 | pages = 116–35 | date = June 2005 | issue = 1 | pmid = 16024755 | doi = 10.1196/annals.1347.008 | bibcode = 2005NYASA1052..116D | s2cid = 46583658 }}</ref> 17α-Estradiol (as the sodium salt of its sulfated form) is a minor component (<10%) of hormone replacement products (such as [[conjugated 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.<ref>{{cite journal | vauthors = Moos WH, Dykens JA, Nohynek D, Rubinchik E, Howell N | year = 2009 | title = Review of the Effects of 17α-Estradiol in Humans: A Less Feminizing Estrogen with Neuroprotective Potential | journal = Drug Development Research | volume = 70 | pages = 1–21 | doi=10.1002/ddr.20284| s2cid = 73114400 }}</ref>

Alfatradiol binds to the [[ERα]] and [[ERβ]] with 58% and 11% of the [[relative binding affinity]] of 17β-estradiol.<ref name="pmid9048584">{{cite journal | vauthors = Kuiper GG, Carlsson B, Grandien K, Enmark E, Häggblad J, Nilsson S, Gustafsson JA | title = Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta | journal = Endocrinology | volume = 138 | issue = 3 | pages = 863–70 | date = March 1997 | pmid = 9048584 | doi = 10.1210/endo.138.3.4979 | doi-access = free }}</ref> However, it has 100-fold lower estrogenic activity relative to estradiol,<ref name="TrüebLee2014">{{cite book | vauthors = Trüeb RM, Lee W |title=Male Alopecia: Guide to Successful Management |url=https://books.google.com/books?id=0ue5BAAAQBAJ&pg=PA93 |date=13 February 2014|publisher=Springer Science & Business Media|isbn=978-3-319-03233-7|page=93}}</ref> which may in part be due to differences in the [[intrinsic activity]] of the two compounds.{{Citation needed|date=September 2016}} On the other hand, alfatradiol has been found to bind to and activate the [[brain]]-expressed [[ER-X]] with a greater [[potency (pharmacology)|potency]] than estradiol, indicating that it may be the predominant [[endogenous]] [[ligand (biochemistry)|ligand]] for the receptor.<ref name="pmid15947006">{{cite journal | vauthors = Toran-Allerand CD, Tinnikov AA, Singh RJ, Nethrapalli IS | title = 17alpha-estradiol: a brain-active estrogen? | journal = Endocrinology | volume = 146 | issue = 9 | pages = 3843–50 | date = September 2005 | pmid = 15947006 | doi = 10.1210/en.2004-1616 | doi-access = free }}</ref> In contrast to estradiol, alfatradiol is not a [[ligand (biochemistry)|ligand]] of the [[G protein-coupled estrogen receptor]] (affinity >10&nbsp;μM).<ref name="pmid26023144">{{cite journal | vauthors = Prossnitz ER, Arterburn JB | title = International Union of Basic and Clinical Pharmacology. XCVII. G Protein-Coupled Estrogen Receptor and Its Pharmacologic Modulators | journal = Pharmacol. Rev. | volume = 67 | issue = 3 | pages = 505–40 | date = July 2015 | pmid = 26023144 | pmc = 4485017 | doi = 10.1124/pr.114.009712 }}</ref>

{{Affinities of estrogen receptor ligands for the ERα and ERβ}}

{{Selected biological properties of endogenous estrogens in rats}}

==Society and culture==

===Generic names===

''Alfatradiol'' is the [[generic term|generic name]] of the drug and its {{abbrlink|INN|International Nonproprietary Name}}.<ref name="Drugs.com" /> It is also known as ''17α-estradiol''.<ref name="Elks2014" />

===Brand names===

Alfatradiol is marketed under the brand names Avicis, Avixis, Ell-Cranell Alpha, and Pantostin.<ref name="Drugs.com" />

===Availability===

Alfatradiol is available in [[Germany]] and several [[Latin America]]n countries, including [[Argentina]], [[Brazil]], and [[Mexico]].

==Research==

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 of [[type 2 diabetes]].<ref name="pmid26809497">{{cite journal | vauthors = Stout MB, Steyn FJ, Jurczak MJ, Camporez JG, Zhu Y, Hawse JR, Jurk D, Palmer AK, Xu M, Pirtskhalava T, Evans GL, de Souza Santos R, Frank AP, White TA, Monroe DG, Singh RJ, Casaclang-Verzosa G, Miller JD, Clegg DJ, LeBrasseur NK, von Zglinicki T, Shulman GI, Tchkonia T, Kirkland JL | display-authors = 6 | title = 17α-Estradiol Alleviates Age-related Metabolic and Inflammatory Dysfunction in Male Mice Without Inducing Feminization | journal = The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences | volume = 72 | issue = 1 | pages = 3–15 | date = January 2017 | pmid = 26809497 | pmc = 5155656 | doi = 10.1093/gerona/glv309 }}</ref>

== See also ==

* [[Alfatradiol/dexamethasone]] (Ell-Cranell Dexa)

* [[Estradiol 17alpha-dehydrogenase|Estradiol 17α-dehydrogenase]]

* [[List of estrogens]]

== References ==

<ref name="WHO">{{cite journal | url = http://apps.who.int/medicinedocs/en/d/Jh2989e/10.html | archive-url = https://web.archive.org/web/20091127140744/http://apps.who.int/medicinedocs/en/d/Jh2989e/10.html | url-status = dead | archive-date = 27 November 2009 | journal = WHO Drug Information | volume = 15 | issue = 3&4 | title = Recommended International Nonproprietary Names (rec. Inn): List 46 | year = 2001 }}</ref>

<ref name="RoteListe">{{cite book| veditors = Hildegard D |title=Rote Liste|edition=2005|at=32&nbsp;369|publisher=Editio Cantor Verlag|location=Aulendorf|language=de|isbn=978-3-87193-306-6|url=https://books.google.com/books?id=zZ5KAQAAIAAJ|year=2005}}</ref>

<ref name="Austria-Codex">{{cite book|title=Austria-Codex| veditors = Jasek W |publisher=Österreichischer Apothekerverlag|location=Vienna|year=2007|edition=2007/2008|volume=4|page=9673|isbn=978-3-85200-181-4|language=de}}</ref>

<ref name="Hunnius">{{cite book| veditors = Berger A, Wachter H |title=Hunnius Pharmazeutisches Wörterbuch|edition=8|publisher=Walter de Gruyter Verlag|year=1998|language=de|page=486|isbn=978-3-11-015793-2|url=https://books.google.com/books?id=WSGmQgAACAAJ}}</ref>

<ref name="Mutschler">{{cite book | vauthors = Mutschler E, Geisslinger G, Kroemer HK, Schäfer-Korting M |title=Arzneimittelwirkungen|publisher=Wissenschaftliche Verlagsgesellschaft|location=Stuttgart|year=2001|edition=8|page=453|isbn=978-3-8047-1763-3|language=de|url=https://books.google.com/books?id=pOM5SQAACAAJ}}</ref>

==External links==

* [https://en.longevitywiki.org/wiki/Alfatradiol_(17α-estradiol) Alfatradiol (17α-estradiol)]

{{Estrogens and antiestrogens}}

{{Androgens and antiandrogens}}

{{Estrogen receptor modulators}}

[[Category:5α-Reductase inhibitors]]

[[Category:Diols]]

[[Category:Estranes]]

[[Category:Estrogens]]

[[Category:Hair loss medications]]