Causes of Hyperandrogenism

As far as hyperandrogenisms due to an excess of androgen production are concerned, tumoral causes and Cushing's syndrome are rare. The most common endocrine disorders are polycys-tic ovary syndrome (PCOS) and non-classic adrenal hyperplasia (NCAH) with 21-hydroxylase deficiency. Hyperandrogenism is associated with high levels of circulating androgens and decreased SHBG levels. PCOS also requires morphological and ultrasound criteria: an increased number of subcapsular follicles and stromal hyperplasia. Plasma levels of 17-hydroxyproges-terone (17-HP) are increased in NCAH. If NCAH is only suspected with moderately increased 17-HP, an adrenocorticotropic hormone (ACTH) test must be performed [1, 6, 7].

On the other hand, hyperandrogenic skin changes ("idiopathic" hirsutism, hypertrichosis in men, most cases of acne, AGA in women but also in men) mostly occur in fact in patients with normal androgen levels. Increased enzyme activities in the peripheral metabolism of steroids, and/or increased sensitivity of AR, both presumed to be subjected to genetic polymorphisms, might account for abnormal responses to androgens. The first possibility in patients with androgen-dependent skin manifestations corresponds to increased metabolic pathways that lead to the transformation of weaker an-

drogens to testosterone, increased 5a reduction to DHT and lower aromatase activity [16].

The second possibility (the two not being mutually exclusive) is directly linked to AR sensitivity. AR is a structurally conserved member of the nuclear receptor superfamily. The amino-terminal domain is required for transcriptional activation and contains a region of polygluta-mine encoded by CAG trinucleotide repeats. In humans the number of CAG repeats is polymorphic. Longer repeat lengths are associated with androgen-insensitivity syndromes. It has been suggested that AR polymorphisms (CAG-repeat lengths) account for AGA, hirsutism and acne, since shorter repeat lengths may be associated with the development of androgen-mediated skin disorders in men and women [17].

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