PubMed2002
Androgenetic alopecia (AGA) is the combined result of an androgen-dependent process and genetic transmission. These characteristics have mainly, if not exclusively, been demonstrated in men and perhaps improperly extended to women. When considering the androgen-dependent process, AGA must only be limited to the androgen receptor areas. In the scalp, these receptors have only been detected in the frontal and vertex areas but never in the temporal or the occipital areas. Male AGA exhibits these clinical features, whereas in women hair loss is rarely limited to this localization, even when large areas of hair loss often appear with age. It is now commonly accepted that male AGA is associated with an increase in 5 alpha reductase activity leading to an increase in local production of dihydrotestosterone. The mechanism by which the local dihydrotestosterone increase leads to hair follicle loss is not clearly demonstrated. Inhibition of cell proliferation in the dermal papilla and a vascular process based on the inhibition in local production of vascular endothelial growth factor (VEGF) have been proposed. The increase in 5 alpha reductase activity is genetic and depends on androgen receptor polymorphism, characterized by a decrease in the number of CAG sequences on the exon 1. Male AGA is associated with an insulin-resistant process and to a higher risk of polycystic ovary in the lineage. Therapeutically, this hormone-dependent process explains the well demonstrated efficacy of 5 alpha reductase inhibitors. In women, except in some rare cases, alopecia is diffuse and the mechanisms are different. Their origin is unknown, and probably ambiguous. Based on an association with Hashimoto's thyroiditis, an auto-immune origin could be suggested in some cases. Alopecia is unaffected by thyroid substitution. Pharmacological doses of oestrogens (pregnancy, contraception) have a beneficial effect on such alopecia, probably through different mechanisms: anti-androgen effect, increased VEGF, proliferative effect of dermal papilla cells. However, it is important to mention that the dermal papilla has an aromatase, particularly in the occipital area, the activity of which has not been assessed in female alopecia. In practice 5 alpha reductase inhibitors are ineffective in women. It is likely that the predominance observed in the frontal and vertex areas, occasionally in elderly women, is a result of the two combined disorders, the almost physiological androgen-dependent hair loss combined with diffuse loss. Pharmacological doses of oestrogens associated with anti-androgen progesterone-like agents are widely used with positive results, but not demonstrated by clinical trials.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗