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Mechanism of androgenic alopecia: Addressing speculations through empirical evidences

Dear Editor, AGA affects half of the middle age male inhabitants, and more than 90% of the old age men (Kabir & Goh, 2013). It affects nearly 50% of the world population and about 51% of the males aged between 40 and 75 years (Lolli et al., 2017). AGA is also observed in women and termed as female pattern hair loss. It is very common and one of the distressing causes of social isolation in women (Price, 2003). Despite several path breaking discoveries, treatment of AGA largely depends on the agents which are accidentally discovered for hair regrowth as a side effect of the same drug, which was developed for other purposes (Ellis & Sinclair, 2008). Dihydrotestosterone (DHT) is the main androgen responsible in AGA. 5AR converts testosterone to DHT, therefore, inhibiting 5AR improves hair growth and slows hair loss. 5AR exists as two isoenzymes: Type 1 and 2 where Type 1 is mainly located in the skin, including hair follicles and sebaceous glands whereas Type 2 is present in the inner root sheath of hair follicles and male genitalia including the prostate (Clarke, 2016; Ellis, Stebbing, & Harrap, 1998). An investigation which was conducted in 12 young women (between 14 and 33 years) and 12 young men (between 18 and 30 years) with AGA highlights the presence of AR, Type 1 and Type 2 5AR, and cytochrome p-450 aromatase in hair follicles. Both genders had increased levels of Type 1 and Type 2 5AR and ARs in frontal hair follicles as compared with that of occipital hair follicles (Price, 2003). Although pharmacological agents like Finestride and Minoxidil exist in the market to manage the AGA-like conditions (Chandrashekar, Nandhini, Vasanth, Sriram, & Navale, 2015; Rumsfield, West, & FiedlerWeiss, 1987), none of them are proved till date for the complete cure of the condition. Finasteride, a Type-2 5AR inhibitor (5ARI), significantly improves hair growth and slows hair loss. It is the most commonly used treatment for AGA. Dutasteride inhibits Type 1 and 2 isoenymes of 5AR and has shown to be more effective than Finasteride in treating AGA (Clarke, 2016; Ellis & Sinclair, 2008). However, major side effects of 5ARIs are sexual dysfunction and breast enlargement. Investigation of Dutasteride and Latanoprost needs extra efforts for making them safe alternative and thorough understanding of the underlying molecular mechanisms like genetics and etiology can revive the hope for future-targeted treatment strategies (Clarke, 2016; Ellis & Sinclair, 2008). Indeed, there is less known regarding the regulation of AR expression, the role of AR blockers in the treatment of AGA cannot be underestimated. Hence, unless our knowledge of the molecular mechanism, etiology of AGA, and suitable treatment targets gain pace in this field, one cannot expect reasonable acceleration in the discovery of targeted pharmaceuticals (Ellis & Sinclair, 2008; Lolli et al., 2017). Here, we sought to draw the attention of dermatologists and formulation scientists toward probable novel ways of AGA treatment. In doing so, we tried to address some of the existing speculations about AGA, which needed to be prioritized. Based on empirical evidences, here we present a deep insight of the major triggers of AGA, it's aetiologies and major anatomical and physiological changes while developing AGA. In addition, a thorough and a clear understanding of the mechanism involved in AGA, its treatment, and major treatment targets, on which formulation scientists and dermatologist working in this area can focus upon, are also highlighted.