The role of genetic predisposition and the influence of sex steroid hormones are indisputable to the pathogenesis of male androgenetic alopecia (MAGA). The role of sex steroid hormones in female pattern hair loss (FPHL) is less known. A good knowledge of the pathophysiology underlying MAGA and FPHL empowers the clinician to confidently counsel patients and make informed therapeutic decisions. Vigorous research in recent years has provided greater insight into the role of genetics and sex steroids in physiological hair growth and cycling, as well as in hair follicle miniaturization, the histological hallmark of MAGA and FPHL. In the present review article directed towards clinicians, we discuss the current understanding of the role of androgens and oestrogens, as well as genetic associations with MAGA and FPHL. We also briefly discuss the interpretation of direct-to-consumer genetic testing for baldness to help clinicians understand the limitations of such tests.

Review CMAJ• Inflammation that destroys the bulge of the outer root sheath destroys the hair follicle and leads to cicatricial alopecia.• Primary cicatricial alopecia is an inflammatory disorder of unknown cause that leads to irreversible hair loss.• The natural history is for the alopecia to extend slowly over the scalp and eventually burn out. The rate of extension and the final severity are extremely variable and difficult to predict.• A number of treatments are used empirically; however, they are not supported by data from clinical trials.

Androgenetic alopecia affects both men and women. In men it produces male pattern hair loss with bitemporal recession and vertex baldness. In women it produces female pattern hair loss (FPHL) with diffuse alopecia over the mid-frontal scalp. FPHL occurs as a result of nonuniform hair follicle miniaturization within follicular units. Diffuse alopecia is produced by a reduction in the number of terminal fibres per follicular unit. Baldness occurs only when all hairs within the follicular units are miniaturized and is a relatively late event in women. 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 have provided a clearer understanding of the early stages of androgenetic alopecia and how the male and female patterns of hair loss are related. FPHL is the most common cause of alopecia in women and approximately one-third of adult caucasian women experience hair loss. The impact of FPHL is predominantly psychological. While men anticipate age-related hair loss, hair loss in women is usually unexpected and unwelcome at any age. Treatment options to arrest hair loss progression and stimulate partial hair regrowth for FPHL include the androgen receptor antagonists spironolactone and cyproterone acetate, the 5α-reductase inhibitor finasteride and the androgen-independent hair growth stimulator minoxidil. These treatments appear to work best when initiated early. Hair transplantation should be considered in advanced FPHL that is resistant to medical treatments. Hair transplantation requires well-preserved hair growth over the occipital donor area. The psychological impact of FPHL may also be reduced by cosmetic products that improve the appearance of the hair. These agents work to minimize hair fibre breakage, improve hair volume or conceal visible bald scalp.

APM degeneration and replacement with fat in AGA has not previously been described. The underlying mechanism remains to be determined. However, we speculate that this phenomenon might be related to depletion of stem or progenitor cells from the follicle mesenchyme, explaining why AGA is treatment resistant.

The arrector pili muscle (APM) consists of a small band of smooth muscle that connects the hair follicle to the connective tissue of the basement membrane. The APM mediates thermoregulation by contracting to increase air-trapping, but was thought to be vestigial in humans. The APM attaches proximally to the hair follicle at the bulge, a known stem cell niche. Recent studies have been directed toward this muscle's possible role in maintaining the follicular integrity and stability. This review summarizes APM anatomy and physiology and then discusses the relationship between the follicular unit and the APM. The potential role of the APM in hair loss disorders is also described, and a model explaining APM changes in hair loss is proposed.

Applying proteomics to the study of congenital and acquired hair shaft disorders can deliver new insights into hair damage and novel strategies to strengthen hair.

The wool follicles of New Zealand Wiltshire sheep can be induced to undergo growth cycles by manipulating circulating prolactin levels. Altered patterns of gene expression through this cycle were examined using differential display, and nine sequence tags for differentially expressed genes were isolated. Four of these tags were identified as fragments of known genes, encoding a wool keratin, KRTAP3.2, a desmosome component, desmoglein 1, an epithelial cell marker, stratifin, and a protein kinase, Clk3. All four genes were shown to be downregulated in telogen skin compared with anagen. In situ hybridization showed that all had localization patterns which included cells that are absent in telogen. The stratifin tag was used to clone a cDNA that incorporated a complete open-reading frame for ovine stratifin. Ovine stratifin is similar to the human form, showing only six single residue differences in the predicted amino acid sequence. Stratifin probably acts as a regulator of other proteins involved in trichocyte cell cycling and differentiation. Clk3 is involved in regulating RNA splicing. KRTAP3.2 and Dsg1 both play structural roles in hair follicles. The other five tags, including two representing genes that were upregulated during catagen, could not be identified by homology. Differential display is an effective means of identifying genes involved in follicle function and, potentially, of genes controlling the growth cycle.

No abstract