Hair and Types of Hair Loss
Hair is amongst the fastest growing tissues of the body, undergoing repetitive and regenerative cyclical changes, with each cycle consisting of telogen (resting), anagen (active) and catagen (physiological involution) stages (Paus and Foitzik, 2004) (Figure 3). During the transition from telogen to anagen, there is stringent regulation of the activation of epithelial bulge stem cells, while transit amplifying (TA) progeny cells arise from the secondary hair germ cells (Tiede et al., 2007). Along the period of the anagen phase, the TA cells display resilient proliferation within the epithelial matrix of the hair follicle. As a result, the end product of the hair cycle (i.e., the bulk of the hair filament) is formed through terminal differentiation of the proliferating trichocytes.
The prime regulatory element of progenitor cell activation, hair matrix cell proliferation, and terminal differentiation of trichocytes is believed to be the dermal papilla of the hair follicle (Plikus et al., 2006). The anagen stage represents the growth stage of the hair cycle, and may last 2 to 6 years. The catagen stage, which generally lasts 1 to 2 weeks, is when transitioning of club hair is observed; as it progresses towards the skin pore, and the dermal papilla begins to separate from the hair follicle. The telogen stage which lasts from 5 to 6 weeks, exhibits a complete dermal papillary separation from the hair follicle. Lastly, the cycle progresses again towards the anagen stage as the dermal papilla joins up with the hair follicle and the hair matrix starts synthesizing new hair.
Androgenetic alopecia (AGA) is the most common form of hair loss in men, affecting almost 50% of the male population (Otberg et al., 2007). As the name suggests, AGA refers to hair loss induced in genetically susceptible individuals due to the effects of androgens such as testosterone. Testosterone is a lipophilic hormone that diffuses across the cell membrane to carry out its function. It is converted to a more active form called dihydrotestosterone (DHT), which is responsible for many of the effects observed in AGA. The enzyme responsible for the conversion of testosterone to DHT is 5α-reductase. Two types of 5α-reductase enzymes are found in body tissues: Type 1, which is prevalent in keratinocytes, fibroblasts, sweat glands, and sebocytes, and Type 2, found in skin and the inner root sheath of hair follicles. DHT acts by binding to its nuclear androgen receptor, which is responsible for regulating associated gene expression (Ghanaat, 2010).
Abnormal androgen signaling is responsible for the disruption of epithelial progenitor cell activation and TA cell proliferation, which forms the essential pathophysiological basis for AGA (Itami and Inui, 2005). The exact genes associated with the process of hair loss are not entirely known, however, some genes implicated in hair growth are known, and include genes for desmoglein, activin, epidermal growth factor (EGF), fibroblast growth factor (FGF), lymphoid-enhancer factor-1 (LEF-1), and sonic hedgehog (Ghanaat, 2010). Presently, amongst the treatment options available, the most commonly used include minoxidil, finasteride, or surgical hair transplantation (Otberg et al., 2007). Recently, the United States Food and Drug Administration (FDA) has approved the use of LLLT as a novel treatment modality for hair loss (Wikramanayake et al., 2012).
Several other forms of hair loss also exist such as telogen effluvium (TE), alopecia areata (AA), and alopecia induced via chemotherapy. AA is an autoimmune inflammatory condition that presents with non-scarring alopecia, where histologic characterizations display intra- or peri-follicular lymphocytic infiltrates composed of CD4+ and CD8+ T-cells (Wikramanayake et al., 2012). AA has two variants, with one being alopecia totalis (complete loss of scalp hair), and the other being alopecia universalis (total loss of body and scalp hair) (Wasserman et al., 2007). The most common forms of treatments for alopecia involve intra-lesional corticosteroids, however, other treatment modalities are also available such as topical and systemic corticosteroids, e.g., minoxidil (used in moderate cases) and anthralin. Contact sensitizers are used when more than half of the scalp is affected.
PUVA treatment, cyclosporine, tacrolimus, and biologics such as alefacept, efalizumab, etanercept, infliximab, and adalimumab are also utilized for the treatment of hair loss (Ghanaat, 2010). TE is a condition where abnormal hair cycling results in excessive loss of telogen hair (Ghanaat, 2010). Some of the common causes that result in TE include acute severe illness, surgery, iron deficiency anemia, thyroid disease, malnutrition, chronic illness, and medications (e.g., contraceptives, lithium and cimetidine). Chemotherapy functions by acting on fast-growing cancer cells and destroying them, but it also results in the destruction of fast-growing somatic cells in the body, such as those of the hair follicles, and thus, results in the induction of alopecia. It is usually observed within 1 to 3 weeks of initiating therapy, where the most profound effects are observed (Trueb, 2009).
Quite recently, lasers have gathered much attention due to their remarkable ability to cause selective hair removal, however, in some instances it has been observed that, lasers can result in undesirable effects on hair growth such as increased hair density, increased color or coarseness, or a combination of these (Moreno-Arias et al., 2002a, 2002b; Vlachos and Kontoes, 2002; Wikramanayake et al., 2012). This phenomenon is known as “Paradoxical Hypertrichosis”, and its incidence varies from 0.6% to 10% (Wikramanayake et al., 2012). It has also been reported that low-powered laser irradiation of small vellus hairs, can cause them to transform into larger terminal hairs (terminalization of vellus hair follicles) (Bernstein, 2005; Bouzari and Firooz, 2006).
The idea that lasers are able to induce hair growth is not something new. In the late 1960s, Endre Mester, a Hungarian scientist, conducted a series of experiments to investigate the ability of the newly developed lasers to cause cancer in mice, using a low-powered ruby laser (694 nm). The laser exposure failed to cause cancer on shaved mice, but it enhanced hair growth (Mester et al., 1968). This fortuitous observation was the first example of “photobiostimulation” using LLLT, and it opened up a new avenue for the field of medicine (Barolet and Boucher, 2008).
Different mechanisms have been proposed in an attempt to explain the effects of LLLT. In one particular study, this ability of lasers (to promote hair growth) was attributed to a side-effect of polycystic ovarian syndrome (PCOS) present in 5 out of 49 females undergoing IPL laser treatment for facial hirsutism (Moreno-Arias et al., 2002a). Another study suggested that, although lasers were responsible for heat generating effects in tissues, the heat produced was not sufficient enough to induce hair follicle thermolysis, however, it may be sufficient to stimulate follicular stem cell proliferation and differentiation by increasing levels of heat shock proteins (HSPs) such as HSP27, which influence the regulation of cell growth and differentiation (Wikramanayake et al., 2012). Some form of sub-therapeutic injury could potentially cause the release of certain factors that could induce follicular angiogenesis, and influence the cycling of cells (Bouzari and Firooz, 2006).
In 2007, the FDA approved LLLT as a possible treatment modality for hair loss (Wikramanayake et al., 2012). Some of the devices that are used for LLLT in hair regrowth are shown in Figure 4. It is believed that LLLT can stimulate re-entry of telogen hair follicles into the anagen stage, bring about greater rates of proliferation in active anagen follicles, prevent development of premature catagen stage, and extend the duration of the anagen phase (Leavitt et al., 2009; Wikramanayake et al., 2012). Although the exact underlying mechanism regarding how LLLT promotes hair growth is not known, several hypotheses have been proposed.
Current data suggests that, the action of LLLT on mitochondria leads to increased adenosine triphosphate (ATP) production, modulation of reactive oxygen species (ROS), and stimulation of transcription factors. These transcription factors, in turn, are responsible for the synthesis of proteins that cause certain down-stream responses leading to enhanced proliferation and migration of cells, modulation of cytokine levels, growth factors and mediators of inflammation, and increased tissue oxygenation (Chung et al., 2012).
In one study, the backs of Sprague Dawley rats were irradiated using a linearly polarized IR laser, and, an up-regulation of hepatocyte growth factor (HGF) and HGF activator was observed (Miura et al., 1999). Another study reported increases in temperature of the skin as well as improved blood flow around areas of the stellate ganglion, following LLLT (Wajima et al., 1996).