done as the hair follicle functions according to an independent growth mechanism called the Hair Growth Cycle. This all important Hair Growth Cycle is comprised of three phases; rapid growth (Anagen), apoptosis driven regression (Catagen), and relative inactivity or rest (Telogen).3
After a period of acute or chronic stress many individuals will experience an increased amount of hair loss. In murine studies, chronic stress was significantly associated with hair growth inhibition, increased granulation of mast cells and perifollicular inflammation.8 Further studies, both in vitro and in vivo, have demonstrated that certain stress-mediating substances such as substance P, adrenocorticotropic hormone, prolactin, and cortisol actually inhibit the growth of hair.9-11
Neural signals have also been demonstrated to modulate hair growth, however this is not essential for the normal function of the hair growth cycle. Moreover, researchers have shown the ability of corticotropin-releasing hormone to directly stimulate isolated hair follicles in humans, with cortisol synthesis and neuroendocrine feedback loops.1
Of particular interest are the steroid hormones cortisone and cortisol, which are released in response to stress. As the research cited above posits the direct effect of cortisol on the hair follicle, a direct correlation between cortisol and the development of hair loss can also be identified.
Cortisol and Cortisol Inhibitors
Studies have indicated a range of side effects on the skin and its structural components resulting from the presence of excess cortisol.12 In fact, the presence of elevated levels of cortisol has been demonstrated in both males and females with androgenetic alopecia, compared to controls.13,14
Measuring the precise effect of cortisol on human connection tissue is not a simple and straightforward task. ‘Hair analysis’, however, is a common method used to measure the presence of external compounds in the body, especially in relation to illicit or harmful chemical substances.15 Hair analysis is widely used since the presence of substances in the hair can be tracked over time, due to the fact that hair grows at a steady rate of approximately 1 cm per month.16 Similarly, this methodology is being applied to measure chronic stress in the body by tracking and quantifying cortisol levels as a biological marker in hair.17
When analysing cortisol measurements in the body, interestingly, low cortisol levels have been shown to exert positive effects. Low levels of cortisol actually stimulate, as well as slow the breakdown of hyaluronan and proteoglycans by approximately 25%. However when cortisol is present at high levels the opposite is true, as it has been shown to reduce the synthesis and accelerate the breakdown of these structural skin components (hyaluronan and Thomproteoglycans) by approximately 40%.18 As proteoglycans and hyaluronan serve the function of attracting and retaining moisture in the skin, the degradation and reduction of these skin components would present as excessively dry skin.12
One known cortisol inhibitor is ketoconazole, an imidazole anti-fungal agent used to treat dandruff and seborrheic dermatitis. The functionality of ketoconazole has been indicated in vivo, and consequently confirmed in vitro, to inhibit the secretion of cortisol. This is done by blocking 11 beta-hydroxylase activity which is then compensated by high levels of adrenocorticotropic hormone in vivo.19
Researchers have studied the effect of using a 2% ketoconazole shampoo long-term, and it was demonstrated that the size and proportion of hair follicles in the anagen phase, as well as hair density, were improved in the case of androgenetic alopecia. The 2% ketoconazole shampoo was also shown to have an additive effect for androgenetic alopecia when used in combination with finasteride.20 The positive effect of this 2% ketoconazole shampoo was later confirmed in a small, open study in which it was concluded that ketoconazole may exert its positive effects on androgenetic alopecia in both an androgen-dependent, as well as androgen-independent manner.21
Proteoglycans and Cortisol
For the hair follicle to function properly according to a normal cycle, specialised cells in the follicle must interact according to intricate signalling mechanisms. A number of research studies conducted between 1991 and 2008 demonstrated that the presence of proteoglycans and glycosaminoglycans play an important role on the normal function and cycling mechanism of the hair follicle.22-28
Proteoglycans are heavily glycosylated proteins that consist of a core protein, together with one or more covalently attached glycosaminoglycan side chains. Glycosaminoglycans are long, unbranched polysaccharides containing a repeating disaccharide unit.29
Specifically, versican is a type of large proteoglycan belonging to the lectican family, and is known as a chondroitin sulfate proteoglycan. Versicans are present in a range of human tissues and comprise one of the main components of the extracellular matrix. This is to provide a loose and hydrated matrix during key events in development and disease. Versicans are known for their role in cell adhesion and are centrally involved in tissue morphogenesis and maintenance. In addition, versicans contribute to the development of a number of pathologic processes including hair follicle cycling.30
Decorin is a proteoglycan from the small leucine-rich proteoglycan gene family, and consists of a protein core with
