INTRODUCTION
The pathogenesis of acne is attributed to a combination of changes in the skin. Many of these changes are dominantly regulated by the sebaceous gland and include increased sebum production, altered lipid composition of sebum, and inflammation.1-3 Insulin-like growth factor-1 (IGF-1), which increases during puberty, stimulates lipogenesis in sebaceous glands and potentiates androgen signaling by inducing 5α-reductase activity and activation of the AR.4 The AR is expressed in the cells of the sebaceous gland (sebocytes), and androgenic hormones have been shown to increase the proliferation and differentiation of sebocytes.5-7 The AR is both a major regulator of the synthesis of a complex group of lipids and is involved in signaling pathways that lead to the production of inflammatory cytokines.6,8 Both P. acnes and the potent androgen dihydrotestosterone (DHT) can stimulate sebocytes to secrete these cytokines.8-10 Comparing gene expression profiles of skin obtained from acne patients and those without acne shows that the majority of upregulated genes are involved in inflammatory processes.11 Consistent with this is the abundance of the inflammatory cytokines IL-1β and IL8 in human acne lesions.12Although several new anti-acne agents that target various processes relevant to acne pathogenesis have completed or are currently in Phase 1 and 2 clinical trials,13 altering sebocyte signaling remains one of the most attractive therapeutic option for treating acne. Currently, the most commonly used sebo-suppressive treatment involves the use of isotretinoin administered orally.14 Another sebo-suppressive acne therapeutic currently in use is the oral androgen inhibitor spironolactone, which is only effective in females and can cause health problems in males.15,16 Finally, the acetyl coenzyme A carboxylase (ACC) inhibitor olumacostat glasaretil (OG) was being developed as an acne treatment based on its ability to inhibit the rate-limiting step of lipid synthesis in sebocytes.17 However, OG failed to meet the designated endpoints in a recent Phase 3 clinical trial.18Despite considerable evidence for the role of excess androgens in the pathophysiology of acne, to date there is no topical androgen inhibitor prescribed to treat acne. Cortexolone 17α-propionate (clascoterone) is a novel AR inhibitor with strong topical antiandrogenic activity and anti-inflammatory properties.19 A pilot study comparing topical creams containing either clascoterone or tretinoin in acne patients demonstrated that clascoterone was well tolerated, more effective than tretinoin at reducing acne lesions, and worked 50% faster than
