Androgenetic alopecia. Modelling progression and regrowth

Androgenetic alopecia (AGA) produces the phenotypes of male pattern hair loss and female pattern hair loss. The pathogenesis of AGA involves hair follicle miniaturization and changes to the hair cycle. Hair follicle miniaturization involves conversion of terminal hairs into secondary vellus hairs. This is recognized in scalp biopsies, unit area trichograms and phototrichograms as a reduction in the number of terminal hairs per cm2 and an increase in the number of vellus hairs per cm2 1. In addition, a small reduction in the total number of hair follicles detectable on scalp biopsy occurs with advancing age 2. The changes in hair cycle dynamics include shortening of anagen duration and an increase in telogen duration. The substage of telogen that is extended in androgenetic alopecia is kenogen. Kenogen is the phase that follows exogen and produces empty follicles. Empty follicle are visible on scalp biopsy but are not detected on phototrichogram. In untreated men and women with androgenetic alopecia, Rushton et al. 3 used serial unit area trichograms to quantify the reduction in total hair count and the change in vellus hair count. The reduction in total hair count is presumed to reflect the increased proportion of hairs in kenogen. An increase in vellus hair count is presumed to reflect miniaturization of terminal into vellus follicles. Fig. 1 Over a 12 month period, Rushton et al. found that the increase in kenogen contributes much more to the overall hair loss than miniaturization. Similarly, when women with FPHL are compared to controls, the reduction in total hair density due to the increase in kenogen is about five times greater than the increase in vellus hairs due to miniaturization. Conversely, when men and women with patterned hair loss are treated, Rushton et al. observed an increase in total hair density presumably due to initiation of anagen in kenogen follicles. Rushton et al. also found that there may be an associated reduction in vellus hair count suggesting that some secondary vellus hairs are enlarging into terminal hairs, reflecting reversal of follicular miniaturization; however, this is not seen in all studies. Interpretation of these changes is difficult as it conflicts with the histological date from Whiting 4. Whiting did serial 4-mm scalp punch biopsies on man and women undergoing blinded treatment with either finasteride or placebo. Among the men being treated with finasteride, he found a mean increase in terminal hairs of 5.4 per biopsy and a reduction in vellus hairs of 3.1 per 4-mm punch biopsy. In the female study, he found no significant difference among females being treated with finasteride and assumed this to indicate finasteride was not effective in treating hair loss in postmenopausal women. One possible explanation for the conflicting trichogram and histology results would be transition of vellus hair in kenogen cycle into anagen would lead to previously undetected vellus fibres being seen on unit area trichograms. This would conceal a reduction in vellus hair count due to reversal of hair follicle miniaturization and lead to an underestimation of the relative contribution of vellus to terminal transition to the improvement in hair density seen with effective treatment. Nevertheless, the rapid improvement in hair density seen with minoxidil treatment suggests that reversal of hair miniaturization is not the most important mechanism of hair regrowth. Rushton's paper makes a useful contribution to our understanding the actual mechanism of both hair loss and hair regrowth in androgenetic alopecia. It allows us to model episodes of increased hair shedding in androgenetic alopecia and periods of rapid progression of hair loss. It complements our understanding of the influence of follicular units on the progression of androgenetic alopecia. So, how can we incorporate these findings into our current model of the pathogenesis of androgenetic alopecia? In the model first proposed by Yazdabadi 5, diffuse hair thinning precedes balding by a number of years. The diffuse thinning is due to a reduction in the number of terminal hair fibres per follicular unit. Baldness occurs only when all terminal hair fibres within the follicular units are lost. Loss of terminal fibres can occur either due to miniaturization or prolongation of kenogen. The concepts of follicular units and primary and secondary hair follicles within follicular units are well established in comparative mammalian studies, particularly in sheep. However, discovery of these structures in the human scalp hair and investigation of the changes in follicular unit anatomy during the development of androgenetic alopecia provide a clearer understanding of the early stages of androgenetic alopecia and how the male and female patterns of hair loss are related. Furthermore, studies of the attachment of the arrector pili muscle (APM) to the hair bulge stem cell reservoir have helped us to develop models to explain why miniaturization of terminal follicles into to vellus follicles is fully reversible in alopecia areata, but only partially reversible in androgenetic alopecia 6. Destruction of the APM and replacement by fat tissue 7 would explain why successful treatment of AGA relies more on the initiation of anagen in kenogen follicles than reversal of miniaturization as described by Rushton 3. The authors have declared no conflicting interests.