Alfatradiol

Not to be confused with 17β-estradiol.

Alfatradiol (INN, or 17α-estradiol, trade names Ell-Cranell Alpha and Pantostin in Germany) is a 5α-reductase inhibitor used topically for the treatment of androgenic alopecia (hair loss) in men and women. It is a stereoisomer of the endogenous steroid hormone 17β-estradiol.

Uses

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. 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.

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. 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.

Contraindications

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.

Adverse effects

Local burning or itching is not an effect of alfatradiol, but of the ethanol in the solvent. The solution can stimulate sebum production.

Chemistry and pharmacology

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 activity depending on its dosage and the tissue it is affecting. 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. 17α-Estradiol has been studied as a therapeutic with potential to treat Alzheimer's and Parkinson's disease and other patients suffering from neurodegenerative diseases. 17α-Estradiol (as the sodium salt of its sulfated form) is a minor component (<10%) of hormone replacement products (such as 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.

Alfatradiol has 100-fold lower estrogenic activity (that is, at ERα) relative to estradiol. However, 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 endogenous ligand for the receptor.

Research

17α-estradiol improved metabolic function, reduced insulin resistance, decreased intra-abdominal fat, and decreased inflammation in old male mice without inducing feminization, suggesting potential future use for type 2 diabetes.

See also

• Alfatradiol/dexamethasone (Ell-Cranell dexa)
• Estradiol 17alpha-dehydrogenase
• Finasteride
• Ketoconazole
• Minoxidil