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Paris - Androgenetic alopecia researchers have recently made important discoveries regarding pathogenic pathways for the hair-loss disorder and possible new approaches to treatment, Antonella Tosti, M.D., said at the World Congress of Dermatology.

Presenting a literature review, Dr. Tosti, professor of dermatology, University of Bologna, Italy, reported that genetic researchers have determined a possible association of androgenetic alopecia with the androgen receptor gene. Strong involvement of genes regulating 5-alpha reductase isoenzymes and the human hairless gene has been ruled out, she said.

In studying hormone-mediated mechanisms, Hoffmann and colleagues determined that steroid sulfatase enzymes, which mediate the transformation of dehydroepiandrosterone sulfate (DHEAS) to dehydroepiandrosterone (DHEA), may be important in androgenetic alopecia. They found that the dermal papilla is a major site of steroid sulfatase expression and that the dermal papillae could use DHEAS to produce 5-alpha dihydrotestosterone, indicating that there is the potential for production of potent androgens within the follicle.

"That is an interesting finding because it suggests a possible role for using steroid sulfatase inhibitors as a novel treatment for androgenetic alopecia. In fact, these researchers reported that the activity of steroid sulfatase was inhibited by estrone-3-O-sulfamate, and that may be a new aspect to investigate," Dr. Tosti said.

Various researchers have provided new evidence about miniaturization that indicates it is not necessarily a gradual process. That finding also has implications for patient management, Dr. Tosti said.

"We used to believe androgenetic alopecia occurred as a consequence of a series of hair cycles producing progressively smaller and smaller hair. However, it seems that miniaturization can occur in a single cycle and hair loss can worsen rapidly, so that delaying treatment can be very deleterious," she explained.

Other studies have focused on identifying early markers for androgenetic alopecia, and in that regard, a report by Choi and colleagues indicates that a high ratio of testosterone to epitestosterone in terminal hair may be a useful predictor. Other investigators have provided evidence that hair shaft thinning may be more important than reduced hair density in the perception of early baldness. Vecchio and colleagues showed that the ratio of parietal to occipital hair density was significantly decreased only in individuals with clinically evident baldness, indicating that that measurement of hair density is not useful in detecting early baldness. Research performed by Dr. Tosti and colleagues, however, points to the potential value of hair diameter diversity as an early diagnostic sign.

Studying androgenetic alopecia in women, Olsen and colleagues described three different clinical patterns, including the new frontal accentuation or "Christmas tree" pattern in which the frontal region is more affected than the region posterior to it. Recognizing that each pattern may represent a different disease points to the possible importance of stratifying clinical trial participants according to alopecia pattern, Dr. Tosti said.

Androgenetic alopecia research has also focused on prepubertal children. Although androgenetic alopecia is classically a disease with an onset after puberty, recently it has been described in preteens. The workup of those children has found that their androgen levels are normal, although a strong genetic predisposition is often present, and follow-up indicates a poor prognosis, as they often go on to develop severe alopecia if left untreated.

"The causes of hair loss in these young patients are not known, but are a subject for future studies. Androgens produced during adrenarche, which occurs before puberty, may be responsible, or perhaps the hair loss is precipitated by androgen exposure from dietary sources," Dr. Tosti said.

The relationship between stress and hair loss was the subject for a study undertaken by Arck and colleagues. They reported that stress may act to trigger hair loss via production of substance P. That event would induce activation of macrophages and mast cells and subsequently release of inflammatory cytokines that may cause apoptosis and inhibit intrafollicular keratinocyte proliferation.

Both topical estrogens and topical latanoprost (Xalatan) have been the subject of preclinical trials. Dr. Tosti observed that while topical estrogen therapy is fairly popular in some European countries, thus far there is only anecdotal data about its efficacy. However, a study conducted by Niiyama et al provided scientific support for its use by showing estrogen could reduce DHT production by dermal papillae in vitro.

"Formal studies evaluating the clinical efficacy of topical estrogen are warranted, as it may be an option for women who cannot be treated with finasteride," Dr. Tosti said.

Latanoprost, a synthetic prostaglandin analogue used topically for glaucoma, was investigated in a preclinical study by Uno and colleagues, where it was shown to have some benefits in the stump-tailed macaque model of androgenetic alopecia. Animals treated with latanoprost 500 µg/mL achieved moderate to marked hair regrowth along with 5 percent to 10 percent conversion of vellus hairs to intermediary or terminal hairs, Dr. Tosti reported.

"Those results are encouraging, but while the stump-tailed macaque is a good model for initial studies of androgenetic alopecia treatments, not all drugs that are effective in those animals work in humans," she






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