Antiandrogens and Androgen Inhibitors

Abstract Circulating androgens can profoundly influence target cutaneous structures such as the pilosebaceous unit (hair follicle and sebaceous gland), and play a central role in the pathogenesis of cutaneous disorders of hyperandrogenism (CHA) which include androgenetic alopecia (AGA), acne vulgaris, and hirsutism. Therapeutically, two main categories of drugs affect androgens and their activity. The first are ‘antiandrogens’ which are agents that block the androgen receptor (AR) and include spironolactone, flutamide, and cyproterone acetate. The second are ‘androgen inhibitors,’ which block androgen synthesis, and include finasteride and dutasteride (these are specific 5-α reductase inhibitors, that inhibit formation of dihydrotestosterone [DHT]), as well as leuprolide, (which is a gonadotropin-releasing hormone (GnRH) agonist, and works at the level of the ovary and pituitary). In this chapter ‘antiandrogens’ is the term used for specific AR blockers, and the term ‘androgen inhibitors’ will be used to distinguish those compounds that work by suppressing or inhibiting the formation of DHT. Other agents such as progestins and combined oral contraceptives (COC) are both antiandrogens and androgen inhibitors. The various drugs discussed in this chapter are categorized by their most important clinical mode of action. This chapter provides an overview of various antiandrogens (drugs that block the AR) and androgen inhibitors (enzyme inhibitors and other mechanisms). How these specific compounds work, their approved and off-label indications, dosing, and adverse effects will be presented. Particular emphasis is given to spironolactone, finasteride, dutasteride, and oral contraceptives.