INTRODUCTION
Androgenetic alopecia (AGA), the most frequent form of alopecia in men and women, is characterized by progressive hair loss in a pattern distribution over the galea aponeurotica of the scalp. Signs of AGA start at any time after puberty, due to increased androgen levels. By the age of 70, 80% of men and up to 40% of women are affected. While not considered a ‘’disease’’ per se, hair loss can have detrimental consequences on the self-esteem and quality of life of affected individuals.1,2
According to the traditional view, the two most important factors in the etiology of AGA include genetic predisposition and androgens, leading to a patterned, non cicatricial alopecia in androgen-dependent areas of the scalp. The past few years, however, have seen a paradigm shift of thought on the nature of AGA, which is now recognized as a multifactorial disorder caused by a complex interplay between the epigenome, androgen metabolism, and ‘nurture’.
Numerous histological, ultrastructural, and immunohistochem-ical studies have shown that miniaturization of hair follicles in AGA is accompanied by microscopic follicular inflammation and fibrosis, pointing to the central role of “micro-inflamma-tion,†a subtle indolent inflammatory process in pattern-type hair loss progression.3-6 This chronic micro-inflammatory state is reinforced by internal and environmental stressors. For ex-ample, sun damage leading to photoactivation of porphyrins produced by Propionibacterium sp. in the pilosebaceous duct can cause oxidative tissue damage as well as the production of radical oxygen species and the release of proinflammatory cy-tokines by keratinocytes.7,8 Disruption of the microbiome in the scalp milieu can lead to overcolonization by Malassezia sp. or Demodex, which further advances the inflammatory response. Other downstream effects, such as activation of apoptotic programs, loss of stem cell differentiation, perturbed microvas-culature of the dermal papilla, toxic metabolite accumulation, and nutrient deficiency, together reinforce the vicious cycle, re-sulting in ongoing hair loss.9
According to the traditional view, the two most important factors in the etiology of AGA include genetic predisposition and androgens, leading to a patterned, non cicatricial alopecia in androgen-dependent areas of the scalp. The past few years, however, have seen a paradigm shift of thought on the nature of AGA, which is now recognized as a multifactorial disorder caused by a complex interplay between the epigenome, androgen metabolism, and ‘nurture’.
Numerous histological, ultrastructural, and immunohistochem-ical studies have shown that miniaturization of hair follicles in AGA is accompanied by microscopic follicular inflammation and fibrosis, pointing to the central role of “micro-inflamma-tion,†a subtle indolent inflammatory process in pattern-type hair loss progression.3-6 This chronic micro-inflammatory state is reinforced by internal and environmental stressors. For ex-ample, sun damage leading to photoactivation of porphyrins produced by Propionibacterium sp. in the pilosebaceous duct can cause oxidative tissue damage as well as the production of radical oxygen species and the release of proinflammatory cy-tokines by keratinocytes.7,8 Disruption of the microbiome in the scalp milieu can lead to overcolonization by Malassezia sp. or Demodex, which further advances the inflammatory response. Other downstream effects, such as activation of apoptotic programs, loss of stem cell differentiation, perturbed microvas-culature of the dermal papilla, toxic metabolite accumulation, and nutrient deficiency, together reinforce the vicious cycle, re-sulting in ongoing hair loss.9
