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Treatment and Prevention of AAS-Induced Hair Loss, Part 2

November 9, 2021 By Peter Bond

In my previous article I discussed the more conventional treatment modalities for androgenetic alopecia, namely the oral and topical versions of finasteride and minoxidil. In this article I’ll go over some of the more novel or experimental ones, such as topical androgen receptor antagonists, platelet-rich plasma (PRP) therapy, Wnt signaling modulators and prostaglandins.

Androgen receptor antagonists

The approach of androgen receptor antagonists is similar to that of 5α-reductase inhibitors such as finasteride and dutasteride: block androgenic action. The mechanism is different however. 5α-reductase inhibitors block the conversion of testosterone to the more potent androgen dihydrotestosterone (DHT). As such, testosterone’s androgenic effect won’t be amplified in scalp tissue. Androgen receptor antagonists block androgenic action by preventing androgens from binding to their receptor. As such, their action is blocked at the level of the androgen receptor itself, and thus it targets virtually all androgens rather than specific ones, as is the case with 5α-reductase inhibitors. The problem with this is that its effects really need to stay localized to the scalp. Blocking overall androgen action in other tissues, such as muscle tissue, is definitely unwanted.

One such drug that’s currently undergoing clinical trials is clascoterone (Breezula). It’s being researched by the pharmaceutical company Cassiopea S.p.A. In vitro research in human dermal papilla cells demonstrated the compound to be effective at inhibiting androgen action [1]. It did so to a greater extent than enzalutamide, another androgen receptor antagonist that’s used in the treatment of prostate cancer, and to a comparable extent as finasteride. It’s affinity for the androgen receptor is relatively low, around a 100-fold lower than DHT’s affinity for the androgen receptor [2]. This isn’t really a problem, you can make up for that by just making sure the hair follicle cells are exposed to a high enough concentration of the compound. However, this does beg the question what its affinity is for other steroid receptors, such as the glucocorticoid receptor. If it doesn’t have a high enough specificity for the androgen receptor, you can get off-target effects by binding to these other receptors. In turn, this can lead to side effects. Again, this isn’t necessarily a problem either if systemic exposure is minimal to non-existent.

In August 2020, the FDA approved clascoterone cream 1 % (Winlevi) for the treatment of acne vulgaris in patients 12 years and older [3]. So it’s in the line of expectations that they’re pursuing approval for androgenetic alopecia too. Indeed, in 2019 they completed a phase 2 study with 404 men for the treatment of androgenetic alopecia (EudraCT 2016-003733-23).

Subjects were treated with a 2.5, 5.0, or 7.5 % 1 mL solution of clascoterone which was to be applied twice daily, or 0.0 (vehicle) and 7.5 % once daily, or vehicle twice daily, for a year. While the results haven’t been published in the scientific literature (yet?), the results can still be viewed online in the EU Clinical Trials Register. Total area hair counts increased significantly compared to the vehicle solution group in all treatment groups. (Mostly because the vehicle solution group saw a significant decrease in total area hair count, reflecting the progression of androgenetic alopecia.) Interestingly, hair growth assessment ratings were similar between all groups, although an increase was reported slightly more often in the treatment groups (56.1 to 61.8 % of subjects compared to 50.0 % in the vehicle-only group). Adverse events were similar across groups.