Alfatradiol is used in form of an ethanolic solution for topical application on the scalp. Similarly to other drugs against alopecia, topical or oral, 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 the hair roots being lost.[6]
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.[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]
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.[10]
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.[10]
Pharmacology
Pharmacodynamics
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 estrogenic activity depending on its dosage and the tissue it is affecting.[11] 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.[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 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.[13]
Alfatradiol binds to the ERα and ERβ with 58% and 11% of the relative 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 the brain-expressed ER-X with a greater potency than estradiol, indicating that it may be the predominant endogenousligand for the receptor.[16] In contrast to estradiol, alfatradiol is not a ligand of the G protein-coupled estrogen receptor (affinity >10 μM).[17]
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.
Notes: Values are mean ± SD or range. ER RBA = Relative binding affinity to estrogen receptors of rat uterinecytosol. Uterine weight = Percentage change in uterine wet weight of ovariectomized rats after 72 hours with continuous administration of 1 μg/hour via subcutaneously 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., not endogenous). b = Atypical uterotrophic effect which plateaus within 48 hours (estradiol's uterotrophy continues linearly up to 72 hours). Sources: See template.
Society and culture
Generic names
Alfatradiol is the generic name of the drug and its INNTooltip International Nonproprietary Name.[2] It is also known as 17α-estradiol.[1]
Brand names
Alfatradiol is marketed under the brand names Avicis, Avixis, Ell-Cranell Alpha, and Pantostin.[2]
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.[18]
^ abMutschler E, Geisslinger G, Kroemer HK, Schäfer-Korting M (2001). Arzneimittelwirkungen (in German) (8 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. p. 453. ISBN978-3-8047-1763-3.
^Jasek W, ed. (2007). Austria-Codex (in German). Vol. 4 (2007/2008 ed.). Vienna: Österreichischer Apothekerverlag. p. 9673. ISBN978-3-85200-181-4.
^Blume-Peytavi U, Kunte C, Krisp A, Garcia Bartels N, Ellwanger U, Hoffmann R (May 2007). "Comparison of the efficacy and safety of topical minoxidil and topical alfatradiol in the treatment of androgenetic alopecia in women". Journal der Deutschen Dermatologischen Gesellschaft. 5 (5): 391–5. doi:10.1111/j.1610-0387.2007.06295.x. PMID17451383. S2CID10260867.
^Orfanos CE, Vogels L (1980). "[Local therapy of androgenetic alopecia with 17 alpha-estradiol. A controlled, randomized double-blind study (author's transl)]". Dermatologica (in German). 161 (2): 124–32. doi:10.1159/000250344. PMID7398983.
^Moos WH, Dykens JA, Howell N (2008). "17α-Estradiol: A Less-Feminizing Estrogen". Drug Development Research. 69 (4): 177–184. doi:10.1002/ddr.20244. S2CID72463459.
^Dykens JA, Moos WH, Howell N (June 2005). "Development of 17alpha-estradiol as a neuroprotective therapeutic agent: rationale and results from a phase I clinical study". Annals of the New York Academy of Sciences. 1052 (1): 116–35. Bibcode:2005NYASA1052..116D. doi:10.1196/annals.1347.008. PMID16024755. S2CID46583658.
^Moos WH, Dykens JA, Nohynek D, Rubinchik E, Howell N (2009). "Review of the Effects of 17α-Estradiol in Humans: A Less Feminizing Estrogen with Neuroprotective Potential". Drug Development Research. 70: 1–21. doi:10.1002/ddr.20284. S2CID73114400.
