ARTICLE: Androgens, Androgen Receptors, and the Skin: From the Laboratory to the Clinic With Emphasis on Clinical and Therapeutic Implications

(some agents FDA-approved for AV), or combination therapy using both agents.4,8,20-27 In the US, use of oral flutamide (not FDA-approved for AV), a competitive inhibitor of AR binding by DHT, has been reported; its use has been limited primarily due to adverse effects and pregnancy-related concerns.4,8,20 In Europe and Canada, cyproterone acetate has long been used as both an oral antiandrogen and progestin that exhibits marked efficacy for AV both as monotherapy and in combination with estrogen as an oral contraceptive, however, it is not available in the US.4,8,20,21 At present, topical antiandrogen therapy is not available. However, topical clascoterone (cortexolone 17α propionate), an AR inhibitor, has completed the formal drug development process and has been submitted to the FDA to be evaluated for approval for treatment of AV.28-30 Clascoterone has been shown to bind the androgen receptor (AR) with high affinity in vitro, inhibit AR-regulated transcription, and antagonize androgen-mediated lipid and inflammatory cytokine production in human sebocytes, with a greater ability to inhibit inflammatory cytokine synthesis from sebocytes when compared to spironolactone.28 These research findings reported with clascoterone further support the significance of direct inhibition of AR in the management of AV, with potential application for other androgen mediated skin disorders.

Advances in understanding of androgen physiology including both central and local tissue mechanisms, enzymatic functions that modulate androgen synthesis and degradation, and AR functionality including the impact of genetic polymorphisms have furthered our understanding of androgen-related diseases states and potential therapeutic options. The above, coupled with increased understanding of receptors and pathways that modulate sebaceous gland activities has also expanded our perspectives on potential therapies for AV. Further elucidation of the functions of androgens and androgen receptors in specific skin disorders can help to shift our focus to the development of therapies that selectively target AR and other receptor pathways that can effectively modify disease and hopefully reduce the risk of adverse effects.

Dr. Del Rosso has served as an advisory board member for Cassiopea, Inc. Dr. Kircik has served as an advisory board member and a consultant for Cassiopea, Inc. Dr. Stein Gold has served as a research investigator and advisor for Cassiopea Inc. Dr. Thiboutot has served as a research investigator and advisory board member for Cassiopea Inc.

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