Androgenetic alopecia: new insights into the pathogenesis and mechanism of hair loss

Abstract

The hair follicle is a complete mini-organ that lends itself as a model for investigation of a variety of complex biological phenomena, including stem cell biology, organ regeneration and cloning. The arrector pili muscle inserts into the hair follicle at the level of the bulge- the epithelial stem cell niche. The arrector pili muscle has been previously thought to be merely a bystander and not to have an active role in hair disease. Computer generated 3D reconstructions of the arrector pili muscle have helped explain why women with androgenetic alopecia (AGA) experience diffuse hair loss rather than the patterned baldness seen in men. Loss of attachment between the bulge stem cell population and the arrector pili muscle also explains why miniaturization is irreversible in AGA but not alopecia areata. A new model for the progression of AGA is presented.

Keywords: Androgenetic; alopecia; follicle.

Figure 1.. Sinclair scale for female pattern hair loss.

Stage 1 is normal. Stage 2 shows widening of the central part. Stage 3 shows widening of the central part and loss of volume lateral to the part line. Stage 4 shows the development of a bald spot anteriorly. Stage 5 shows advanced hair loss.

Figure 2.. Hair shedding scale.

Women are asked which image best corresponds to the amount of hair shed on an average day. Grades 1 to 4 are considered normal for women with long hair. Grades 5 and 6 indicate excessive shedding. Seventy percent of women with female pattern hair loss have excessive shedding.

Figure 3.. Horizontal section of skin biopsy from a hairy scalp showing features of early androgenetic alopecia.

Follicles exist within follicular units comprising arrector pili muscle, sebaceous gland, and derived secondary hairs, some of which have miniaturized to become secondary vellus hairs. The image in the upper right depicts the level of the follicle where the horizontal sections have been cut.

Figure 4.. Normal scalp.

Multiple hair fibres can be seen to emerge from a single infundibulum.

Figure 5.. Horizontal section of skin biopsy from a hairy forearm showing follicles to exist singly or in groups of three, known as Mejeres trios.

Figure 6.. In androgenetic alopecia, a reduction in the number of hairs per follicular unit precedes the development of baldness.

Figure 7.. In telogen effluvium and also alopecia areata, the arrector pili muscle (red) can be shown to be attached to the hair follicle (purple).

( a) 3-dimensional reconstruction of the follicular unit with the muscles coloured red and follicles blue rotated to the left and ( b) to the right.

Figure 8.. In androgenetic alopecia, the proximal arrector pili muscle (red) is progressively replaced by adipose tissue (yellow) and loses its attachment to the hair follicle bulge (purple).

Figure 9.. Reduction in dermal papilla cell numbers as an indirect result of changes to the dermal sheath.

The sheath cells (solid cells) that surround the follicle are an integral part of the follicle dermis ( a). If they are functionally lost (dotted cells indicated by arrows) from the follicle ( b), then dermal papilla cells (outline only) move from the papilla to replace them ( c). As a result, the papilla and the follicle become smaller. Reproduced with permission from John Wiley & Sons, Inc. .

Figure 10.. Scalp follicles exist as compound follicular units.

In androgenetic alopecia, miniaturization occurs initially in the secondary follicles. This leads to a reduction in hair density that precedes visible baldness. Bald scalp becomes visible only when all of the hairs within a follicular unit are miniaturized. With miniaturization, the muscle initially loses attachment to the secondary follicles. When primary follicles eventually miniaturize and lose muscle attachment, the hair loss becomes irreversible.